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J Renin Angiotensin Aldosterone Syst. Author manuscript; available in PMC Sep 1, 2012.
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PMCID: PMC3146958

25-hydroxyvitamin D is Associated with Plasma Renin Activity and the Pressor Response to Dietary Sodium Intake in Caucasians

Anand Vaidya, M.D.,1,3 John P. Forman, M.D., M.Sc.,2,3 Paul N. Hopkins, M.D., MSPH,4 Ellen W. Seely, M.D.,1,3 and Jonathan S. Williams, M.D., M.M.Sc.1,3



Concentrations of 1,25-hydroxyvitamin D have been positively associated with dietary sodium and salt-sensitivity (SS) of blood pressure (BP), and inversely with plasma renin activity (PRA). We investigated the association between PRA and 25-hydroxyvitamin D (25OHD), the most clinically relevant vitamin D metabolite, and whether 25OHD associates with SS of BP in renin phenotypes of hypertension.


We performed cross-sectional analyses on 223 Caucasian subjects with hypertension maintained in high and low dietary sodium balance. Subjects were distinguished as having low-renin (LR) or normal-renin (NR) hypertension. Multivariable linear regression was used to evaluate adjusted relationships.


Increasing 25OHD concentrations were inversely associated with PRA (p<0.05) on both salt diets. Furthermore, 25OHD was associated with SS of BP in LR hypertension (β=0.62, p=0.04), but not in NR hypertension (β=0.06, p=0.59). In an adjusted multivariable interaction model, renin status (LR vs NR) was a significant effect modifier of the relationship between 25OHD and SS of BP (p=0.04).


Our findings suggest that 25OHD is inversely associated with PRA and positively associated with SS of BP in LR hypertension subjects. These results extend and support prior evidence indicating an interaction between dietary sodium, the RAS, and vitamin D that influences BP in hypertension.



Salt-sensitivity (SS) of blood pressure (BP) in HTN is a well described phenotype whose pathophysiology remains incompletely understood [1, 2]. Plasma renin activity (PRA) and SS of BP have both been linked to 1,25-dihydroxyvitamin D (1,25OHD) concentrations [36]; however, the clinically relevant vitamin D metabolite 25-hydroxyvitamin D (25OHD) has not been investigated in the same manner.

Prior work has recognized intra-cellular calcium concentrations as an important determinant of BP responsiveness and HTN [7]. Resnick and others demonstrated that the flux of calcium into vascular smooth muscle cells may be facilitated by 1,25OHD; broadening the pathophysiology of SS in HTN to include considerations of salt- and calcium-regulatory hormones [8, 9]. An inverse relationship between circulating 1,25OHD and plasma renin activity (PRA) has been observed, whereby increased production of 1,25OHD was associated with lower PRA [35]. Furthermore, dietary salt loading was associated with an increase in circulating 1,25OHD concentrations; individuals with the greatest salt-induced increases in 1,25OHD concentrations were those who exhibited the greatest BP response to salt [4, 5, 1012]. Some studies suggested that these continuous relationships between indices of calcium homeostasis and BP were restricted to individuals with a low-renin phenotype of HTN [13, 14].

Since intra-cellular calcium concentrations are also associated with an inhibition of renin secretion in juxtaglomerular cells [15, 16], prior investigators hypothesized that the pressor response to salt in HTN was dependent on the interplay between vitamin D, salt, and the renin-angiotensin system (RAS), resulting in regulation of PRA, vascular smooth muscle intra-cellular calcium, and thus determination of BP responses to salt [5, 12]. Since those studies were published about 20 years ago, little research has continued to explore the role of vitamin D in the pathophysiology of SS in HTN. In the last decade, Li et al. provided convincing support for vitamin D as a renin antagonist in animal experiments [1720]. We recently demonstrated an inverse relationship between 25OHD and vascular RAS activity [21, 22]; supporting previous observations that vitamin D may inhibit the RAS [3, 5, 18].

Given the epidemic prevalence of 25OHD deficiency worldwide [2325] in concert with evidence of an inverse association between vitamin D and renin [3, 4, 17, 18, 21], we investigated the association between 25OHD and PRA under dietary sodium balance in HTN. Since vitamin D is associated with SS of BP [4, 5, 1012, 26], and BP regulation in low-renin HTN [13, 14], we also evaluated whether associations between the precursor substrate 25OHD and the pressor response to salt differed according to renin phenotypes of HTN.


Study Population

This cross-sectional analysis was performed on data gathered from subjects studied in the International Hypertensive Pathotype (HyperPath) Consortium, which has previously been described[21, 27, 28]. The HyperPath Consortium has been an on-going, multi-site study, aimed at investigating the pathophysiologic and genotypic mechanisms involved in hypertension and cardiovascular diseases. Participants were studied at four collaborating centers: Brigham and Women’s Hospital (Boston, MA), University of Utah Medical Center (Salt Lake City, UT), Vanderbilt University Hospital (Nashville, TN), and Hôpital Européen Georges Pompidou (Paris, France).

Subjects with chronic kidney disease, coronary heart disease, heart failure, suggested or known causes of secondary hypertension, and active malignancy were not enrolled in the HyperPath study. Enrolled subjects were classified as having hypertension if they had an untreated seated diastolic blood pressure (DBP) > 100 mmHg, a DBP > 90 mmHg with one or more antihypertensive medications, measured as the average of three readings with standard manual sphygmomanometer, or the use of two or more antihypertensive medications. Study procedures included dietary sodium modulation to maintain low-sodium (LS) and high-sodium balance (HS) in sequence.

Following the original study, 25OHD measurements were performed on the available frozen plasma of all subjects with hypertension. For the purpose of this current cross-sectional analysis, inclusion was restricted to non-diabetic Caucasians classified as having hypertension, successfully maintained in both HS and LS balance per study protocols, and with available 25OHD measurements (n=223). This particular population of hypertensives was pre-selected from the overall HyperPath cohort since race [2931] and diabetes [27, 3234] may confound RAS physiology.

The HyperPath Study Protocol

The original HyperPath study protocol, which all subjects included in this analysis completed, was designed to minimize notable confounders of the RAS. To avoid interference with RAS assessment, participants taking angiotensin converting enzyme inhibitors, angiotensin receptor blockers, or mineralocorticoid receptor antagonists, were withdrawn from these medications three months before study initiation. Beta-blockers were withdrawn one month before study initiation. If needed for blood pressure control, subjects were treated with amlodipine and/or hydrochlorothiazide; however, these medications were stopped three weeks prior to study initiation.

Following at least 3 weeks of full medication washout, subjects were maintained in LS (≤10 mmol/24h), and then HS (≥200 mmol/24h) for 5–7 days each with meals provided by the institutional Clinical Research Center (CRC). Both study diets also included fixed quantities of potassium (80 mmol/day) and calcium (1000mg/day). After each diet phase, participants were admitted to the CRC and maintained in a supine position overnight. External sodium balance and diet compliance were confirmed upon admission to the CRC with a 24-hr urine creatinine and sodium excretion of ≥ 150 mmol for HS, and ≤ 30 mmol for LS. For each diet phase, baseline blood sampling was obtained in the morning, stored at −20 C without preservatives until assayed, and used to measure PRA. Baseline blood pressure was determined while supine between the hours of 8:00 AM and 10:00 AM, following 10 hours of overnight rest using the average of five readings from a Dinamap automated device (Critikon, Tampa, FL). Individuals who exhibited a ≥ 10 mmHg difference in SBP between HS and LS diets (HS SBP – LS SBP) were defined as having SS of BP. Those who exhibited a < 10 mmHg difference in SBP between diets were classified as having salt-resistant (SR) BP. The difference in SBP between HS and LS diets (ΔSBP) was also analyzed as a continuous variable. Study protocols were approved by the Human Subjects Committees/Institutional Review Boards of each location, and informed written consent was obtained from each subject.

Biochemical Assessments

All 223 subjects in this analysis had plasma 25OHD levels measured at baseline using the Diasorin corporation assay. PRA was measured in the morning following overnight supine rest on both LS and HS balance using the Diasorin assay. Per our prior convention, subjects whose PRA rose to 2.4 ng/mL/hr or higher with upright posture in LS balance were defined as having normal-renin (NR) HTN, while those whose PRA remained less than 2.4 ng/mL/hr were defined as low-renin (LR) HTN [35, 36]. All blood samples were processed and stored at one central laboratory (Brigham and Women’s Hospital site).

Statistical Methods

Analyses were performed to evaluate whether 25OHD was associated with PRA, and subsequently whether renin phenotype in HTN influenced the relationship between 25OHD and the BP response to dietary salt intake.

Demographic data are presented as mean values ± standard deviation (SD) for normally distributed data, median values and interquartile ranges for non-normally distributed data, or percentages for categorical data. Student’s t-tests were used to compare means between independent populations with normal distributions, and the non-parametric Wilcoxon Ranks test was used for non-normally distributed data (PRA measurements). Fisher exact testing was used to detect statistical differences between categorical group frequencies. Multivariable linear regression was employed to test the continuous association between 25OHD and ΔSBP, and to test the relation between 25OHD and PRA, where 25OHD was categorized by clinically relevant values (<15, 15–30, ≥30 ng/mL).

Given prior suggestions that renin regulation in HTN may influence the association between vitamin D and the BP response to salt [3, 4, 13, 14], we hypothesized that the relationship between 25OHD and ΔSBP may depend on renin status in HTN. Thus, we analyzed this relationship according to renin status (LR or NR). To evaluate whether renin status was a significant effect modifier of the relationship between 25OHD and ΔSBP between HS and LS diets, we used a multivariable adjusted interaction model including age, sex, BMI, renin subgroup status (LR or NR), and an interaction term between 25OHD and renin subgroup status. The level for significance for all tests conducted was set at α=0.05, with all reported p-values as two-tailed. Data analyses were performed using SAS statistical software, v9.1 (Cary, NC).


25OHD and PRA in the Total Study Population

The mean 25OHD concentration in the total study population was in the insufficient range (22.5 ng/mL; SD=8.8) based on current clinical consensus [24]. Approximately two-thirds of the hypertensive population exhibited SS of BP, and as expected this group was associated with older age, female sex, and lower PRA, when compared to those with SR BP [3741] (Table 1). There were no differences in 25OHD levels between SS groups in the total study population which was comprised of heterogeneous renin phenotypes.

Table 1
Hypertensive study population categorized by those with salt-sensitivity of blood pressure (SS BP) and those with salt-resistant blood pressure (SR BP). Results reported as means (SD), median (interquartile ranges), or percentages. [BMI=body-mass index; ...

We investigated the relationship between 25OHD and PRA using linear regression. An inverse association between 25OHD status and PRA was observed in both HS and LS balance (Figures 1A and 1B). After controlling for age, sex, BMI, and SBP in multivariable modeling, higher 25OHD concentrations continued to predict reduced PRA, and this relationship was independent of dietary sodium balance (p-trend < 0.05 for HS and LS).

Figure 1
The relationship between plasma renin activity and categories of 25-hydroxyvitamin D (25OHD) in the total study population in (A) high dietary salt balance and (B) low dietary salt balance, depicted as means (bars) with standard error of means (whiskers). ...

25OHD and the Pressor Response to Salt Intake by Renin Status

Since the relationship between vitamin D and the BP response to salt was expected to be influenced by renin status [3, 4, 13, 14], we analyzed this relationship separately in the LR (n=43) and NR (n=180) HTN subgroups. Consistent with demographics in the entire study population, approximately two-thirds of each subgroup exhibited SS of BP (66% in LR, and 62% in NR). Individuals with LR were older than those with NR HTN (LR: 51.4 [SD=6.2] vs. NR: 48.4 [SD=8.4] years, p=0.03), and with slightly lower BMI (LR: 26.7 [SD=2.8] vs. NR: 27.9 [SD=3.6] kg/m2, p=0.04). Both groups had similar mean 25OHD concentrations, that were in the insufficient range (LR: 22.7 [SD=9,1] vs. NR: 22.5 [SD=8.8] ng/mL, p=0.86), and displayed no significant difference in their pressor response to salt (LR: 18.1 [SD=16.5] vs. NR: 14.9 [SD=15.3] mmHg, p=0.27).

In subjects with LR HTN, SS of BP was associated with significantly higher 25OHD levels in comparison to salt resistance (Figure 2A). In contrast, salt-sensitive status displayed no association with 25OHD levels in subjects with NR HTN (Figure 2B). These dichotomous relationships were further characterized using linear models which demonstrated a notable positive trend between increasing 25OHD concentrations and the pressor response to salt intake in the LR HTN subgroup (β=0.54, p=0.058) (Figure 3), but not in the NR HTN subgroup (β=0.06, p=0.59). After multivariable adjustment for age, sex, and BMI, 25OHD remained an independent and significant predictor of ΔSBP in subjects with LR HTN (β=0.62, p=0.04). This multivariable model accounted for 15.1% of the variability in ΔSBP, with 25OHD explaining more than two-thirds of the variance in ΔSBP (Table 2). When the interaction between renin subgroup status and 25OHD was evaluated in an adjusted interaction model, renin status was a significant effect modifier of the relationship between 25OHD and the BP response to salt intake (p=0.04).

Figure 2
Box plots describing the distribution of 25-hydroxyvitamin D (25OHD) by salt-sensitivity status (SS BP=salt-sensitivity of blood pressure, SR BP=salt-resistant blood pressure) for (A) low-renin hypertension and (B) normal-renin hypertension subsets. Boxes ...
Figure 3
The univariate relationship between 25-hydroxyvitamin D (25OHD) and the pressor response to salt (ΔSBP) in subjects with low-renin hypertension (β=0.54, p=0.058).
Table 2
Multivariable adjusted relationships between 25OHD, and other relevant variables, and the pressor response to salt in LR hypertension. Results are ordered by magnitude of standardized effect estimates.


Extending the work of others, we hypothesized that 25OHD, the precursor to active 1,25OHD and clinically relevant marker of vitamin D status, would be associated with plasma renin activity independent of salt status. Furthermore, we evaluated whether 25OHD was associated with the pressor response to salt by renin subgroups in HTN. In this cross-sectional study, we analyzed Caucasian subjects with HTN, off all BP medications, and evaluated for salt-sensitivity of BP after maintenance in HS and LS balance. We observed that increasing 25OHD concentrations were associated with lower PRA under both salt conditions, and additionally noted a significant positive relationship between 25OHD and the BP response to salt that was dependent on LR status. These findings support the hypotheses that vitamin D may function as an endogenous renin antagonist, and play a role in determining the pressor response to salt.

Our findings are consistent with and extend the work of others. First, we observed a significant, and independent, inverse relationship between increasing 25OHD concentrations and PRA. These findings are notable in supporting prior human investigations implicating vitamin D in the regulation of renin [3, 4, 6], and animal studies strongly suggesting that vitamin D behaves as an endogenous inhibitor of renin expression [17, 18]. Similar to our observations, Tomaschitz et al. recently demonstrated an inverse relationship between plasma renin concentrations and both 25OHD and 1,25OHD after multivariable adjustments [42]; however, subjects in that cross-sectional study were of mixed HTN and diabetes status, and were analyzed on ad lib anti-hypertensive therapy and ad lib dietary sodium, all of which are significant confounders of the RAS. Our findings substantiate their observations as we exclusively studied non-diabetic subjects with HTN, withdrawn from anti-hypertensive medications, and maintained in strict sodium balance and fixed dietary calcium. In this manner, we detected an inverse relationship between 25OHD and PRA that was evident irrespective of the controlled sodium intake. We also employed multivariable linear regression to control for potentially confounding variables. This finding may have notable implications for clinical medicine; if vitamin D is in the causal pathway to lower PRA, it could be beneficial in treatment of hypertension, cardiovascular and renal diseases [6, 43, 44].

Prior investigators proposed that the relationship between calcium-vitamin D homeostasis and BP may be most evident in LR HTN [13, 14]. Given this observation, and that vitamin D concentrations are inversely associated with PRA and renin phenotype status [3, 4, 42], we subsequently evaluated the relationship between 25OHD and the pressor response to salt. Based on the expectation that a notable association between 25OHD and ΔSBP may not be evident in the combined population where renin phenotypes are heterogeneous, we analyzed this relationship separately in the renin subgroups which were defined via a dichotomous response by PRA to upright posture in LS, as per our prior convention [35, 36]. Higher 25OHD concentrations in LR HTN were independently associated with increased pressor responses to salt; this association was absent in NR HTN. After multivariable analysis, the positive association between 25OHD and the pressor response to salt in the LR sub-group was only marginally significant (p=0.04); this may have been a ramification of our small sample size (n=43). However, when evaluated quantitatively in an adjusted interaction model including all 223 subjects, renin status was a significant effect modifier of the relationship between 25OHD and the change in SBP with salt. This may support the possibility that vitamin D may interact with the RAS to predict the pressor response to salt.

Despite consistent observations establishing salt-sensitivity of BP as a prevalent phenotype in HTN, the pathophysiology of the pressor response to salt remains poorly understood. Prior studies suggest that the BP response to salt is dependent on an interaction between the RAS and vitamin D which determines vascular smooth muscle calcium concentrations, and consequently smooth muscle contractility and vascular tone [7, 8, 1012]. Salt-induced BP elevations have been associated with salt-induced increases in 1,25OHD levels; salt loading results in an increased production of active vitamin D in those individuals who display SS of BP [35]. Furthermore, the observation that calcium concentrations within juxtaglomerular cells inhibit renin release provides another mechanism supporting the association between vitamin D concentrations and low-renin status and reduced activity of renin [3, 4, 15, 16].

At first glance, our current findings associate higher vitamin D status with lower PRA but also increased SS of BP in this low-renin setting, suggesting that suppression of the RAS and sodium retention is associated with higher 25OHD levels. This interpretation may contradict emerging hypotheses that higher vitamin D concentrations reduce BP [6, 45, 46]. On the other hand, the exact relationship between vitamin D, the RAS, sodium balance, and vascular smooth muscle tone may not be this simple, and likely involves many factors implicated by others, but not investigated in our study (ionized calcium, intra- and extra- cellular calcium concentrations, parathyroid hormone, and 1,25OHD) [35, 10, 12, 13, 4749]. Additionally, Imaoka et al. observed that hypertensive women had lower PRA when compared to normotensive women, but also lower 25(OH)D levels; they did not see the same inverse relationship between 25(OH)D and PRA we did [50]. However, the findings of Imaoka et al. may not directly translate to ours since they compared hypertensive women with normotensives, while we specifically focused within the hypertensive phenotype. Although these prior studies proposed a unique and complex interplay between calcium- and sodium-regulating hormones, it remains to be determined whether the actions of vitamin D in this process are to promote, or inhibit, hypertension. Rather, the sum of prior evidence is limited to suggesting that intra-cellular calcium concentrations may be influenced by vitamin D and the RAS, and this interface is fundamental in determining renin activity and the BP response to salt [8, 11, 12, 15, 16].

Our results may shed light on the interaction between salt, calcium, the RAS, and calcium-regulating hormones in predicting BP: the pressor response to salt may depend on a low renin state combined with sufficient vitamin D availability. Furthermore, the concept that LR HTN is strongly associated with salt-sensitivity of BP may need to be re-evaluated to include consideration of vitamin D and calcium homeostasis [1]. Our findings are notable in that they associate 25OHD with the same parameters previously associated with 1,25OHD (PRA and SS of BP) and with the same direction of association. In this regard, 25OHD and 1,25OHD may both serve as barometers of vascular tone in the setting of salt-loading conditions in HTN.

Our results must be interpreted within the context of our study design. First, this analysis was cross-sectional, and thus cannot prove causality or directionality of associations. Our study was not designed to distinguish the mechanism by which vitamin D influences PRA or SS of BP; it provides association data supporting vitamin D as a potential antagonist of PRA and again implicates it in the complex relationship between dietary sodium and BP. Whether vitamin D supplementation dampens or enhances the pressor response to salt is unclear; our findings merely suggest that an interplay between these factors may exist, and warrants more investigation. Though we demonstrated continuous associations between 25OHD and PRA, and between 25OHD and the ΔSBP in LR HTN, we are aware that our phenotyping convention used to define LR and NR status may differ from those used by others; thus our findings may not directly translate to other classifications of LR HTN.

Parathyroid hormone has been associated with HTN, vascular disease, and the RAS [5156]; however, whether its role is independent of vitamin D metabolites remains unresolved [57]. Our study design controlled for dietary sodium and calcium intake, but we did not have ionized calcium, parathyroid hormone, or 1,25OHD measurements that could have shed further insight on potential interacting mechanisms with the RAS and SS HTN, and thus cannot comment on whether our observed association were independent of these factors. However, our findings support prior observations, and raise new questions into the interplay between vitamin D, the RAS, and BP responses to salt. The generalizability of our findings is limited to the population we analyzed, a relatively homogenous group of hypertensive Caucasians without diabetes; this demographic restriction allowed for more reliable results since race [2931] and diabetes [27, 3234] are potential confounders of the RAS. Though our study design controlled for many major confounders of the RAS, several other factors that are known (estrogen status, stress, sympathetic nervous system activity) or unknown to affect the RAS may have influenced our measurements [58, 59]. We have previously observed similar inverse associations between increasing 25OHD and PRA that were not statistically significant; this discrepancy may be due to the fact that they were performed in smaller sample sizes with log-linear analyses, and in a population of normotensives in contrast to our current focus on hypertensives [21, 22].


Although the pressor response to salt remains a poorly understood phenomenon, suggestive evidence implicates an interaction between the RAS and calcium-regulating hormones in the mechanism of SS of BP. Vitamin D metabolites, including 25OHD, are inversely associated with PRA and additionally may be involved in determining the BP response to salt in LR hypertensives. The classification of SS of BP in HTN may warrant consideration of calcium and vitamin D status in addition to salt balance and evaluation of the RAS, especially in LR HTN. Future studies to investigate these complex and evolving relationships are needed.


We would like to thank the staff of the Clinical Research Center’s at our collaborating institutions, including the Brigham and Women’s Hospital, the Centre Investigation Clinique, Hôpital Européen Georges Pompidou, the University of Utah Medical Center, and Vanderbilt University Hospital. Funding support courtesy of National Institutes of Health grants K23 HL04236-03 (JSW), K08 HL079929 (JPF), K24 HL096141 (EWS), F32 HL104776-01 (AV), and UL1 RR025758 Harvard Clinical and Translational Science Center, from the National Center for Research Resources and M01-RR02635, Brigham & Women’s Hospital, General Clinical Research Center, from the National Center for Research Resources. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Library of Medicine, the National Institutes of Health or the National Center for Research Resources.



The authors have nothing to disclose.


1. Weinberger MH. Salt sensitivity of blood pressure in humans. Hypertension. 1996 Mar;27(3 Pt 2):481–90. [PubMed]
2. Johnson RJ, Herrera-Acosta J, Schreiner GF, Rodriguez-Iturbe B. Subtle acquired renal injury as a mechanism of salt-sensitive hypertension. N Engl J Med. 2002 Mar 21;346(12):913–23. [PubMed]
3. Resnick LM, Muller FB, Laragh JH. Calcium-regulating hormones in essential hypertension. Relation to plasma renin activity and sodium metabolism. Ann Intern Med. 1986 Nov;105(5):649–54. [PubMed]
4. Resnick LM, Nicholson JP, Laragh JH. Calcium metabolism in essential hypertension: relationship to altered renin system activity. Fed Proc. 1986 Nov;45(12):2739–45. [PubMed]
5. Burgess ED, Hawkins RG, Watanabe M. Interaction of 1,25-dihydroxyvitamin D and plasma renin activity in high renin essential hypertension. Am J Hypertens. 1990 Dec;3(12 Pt 1):903–5. [PubMed]
6. Vaidya A, Forman JP. Vitamin D and Hypertension: Current Controversies and Future Directions. Hypertension. 2010 epub October.
7. Erne P, Bolli P, Burgisser E, Buhler FR. Correlation of platelet calcium with blood pressure. Effect of antihypertensive therapy. N Engl J Med. 1984 Apr 26;310(17):1084–8. [PubMed]
8. Shan J, Resnick LM, Lewanczuk RZ, Karpinski E, Li B, Pang PK. 1,25-dihydroxyvitamin D as a cardiovascular hormone. Effects on calcium current and cytosolic free calcium in vascular smooth muscle cells. Am J Hypertens. 1993 Dec;6(12):983–8. [PubMed]
9. Nicholson JP, Resnick LM, Cigarroa J, Marion D, Vaughan ED, Jr, Laragh JH. The pressor effect of sodium-volume expansion is calcium mediated. Am J Hypertens. 1991 Nov;4(11):904–8. [PubMed]
10. Resnick LM, Nicholson JP, Laragh JH. The antihypertensive effects of calcium channel blockade: role of sodium and calcium metabolism. J Cardiovasc Pharmacol. 1988;12 (Suppl 6):S114–6. [PubMed]
11. Resnick LM. Calciotropic hormones in human and experimental hypertension. Am J Hypertens. 1990 Aug;3(8 Pt 2):171S–8S. [PubMed]
12. Resnick LM. Calciotropic hormones in salt-sensitive essential hypertension: 1,25-dihydroxyvitamin D and parathyroid hypertensive factor. J Hypertens Suppl. 1994 Jan;12(1):S3–9. [PubMed]
13. Resnick LM. Uniformity and diversity of calcium metabolism in hypertension. A conceptual framework. Am J Med. 1987 Jan 26;82(1B):16–26. [PubMed]
14. Lind L, Wengle B, Wide L, Ljunghall S. Reduction of blood pressure during long-term treatment with active vitamin D (alphacalcidol) is dependent on plasma renin activity and calcium status. A double-blind, placebo-controlled study. Am J Hypertens. 1989 Jan;2(1):20–5. [PubMed]
15. Naftilan AJ, Oparil S. The role of calcium in the control of renin release. Hypertension. 1982 Sep–Oct;4(5):670–5. [PubMed]
16. Beierwaltes WH. The role of calcium in the regulation of renin secretion. Am J Physiol Renal Physiol. 2010 Jan;298(1):F1–F11. [PMC free article] [PubMed]
17. Li YC, Kong J, Wei M, Chen ZF, Liu SQ, Cao LP. 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002 Jul;110(2):229–38. [PMC free article] [PubMed]
18. Li YC. Vitamin D regulation of the renin-angiotensin system. J Cell Biochem. 2003 Feb 1;88(2):327–31. [PubMed]
19. Zhang Y, Deb DK, Kong J, Ning G, Wang Y, Li G, et al. Long-Term Therapeutic Effect of Vitamin D Analog Doxercalciferol on Diabetic Nephropathy: Strong Synergism with AT1 Receptor Antagonist. Am J Physiol Renal Physiol. 2009 Jun;17 [PMC free article] [PubMed]
20. Zhang Y, Kong J, Deb DK, Chang A, Li YC. Vitamin D Receptor Attenuates Renal Fibrosis by Suppressing the Renin-Angiotensin System. J Am Soc Nephrol. 2010 Apr 8; [PMC free article] [PubMed]
21. Forman JP, Williams JS, Fisher ND. Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans. Hypertension. 2010 May;55(5):1283–8. [PMC free article] [PubMed]
22. Vaidya A, Forman JP, Fisher ND, Williams JS. Vitamin D Deficiency Blunts Vascular Sensitivity to Angiotensin II in Obesity. The Journal of Clinical Hypertension. 2010;12(Supplement 1):A1–A165.
23. Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, et al. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005 Jun;90(6):3215–24. [PubMed]
24. Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266–81. [PubMed]
25. Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008 Apr;87(4):1080S–6S. [PubMed]
26. Kotchen TA, Ott CE, Whitescarver SA, Resnick LM, Gertner JM, Blehschmidt NG. Calcium, parathyroid hormone, and vitamin D in the “prehypertensive” Dahl salt-sensitive rat. Am J Hypertens. 1990 Aug;3(8 Pt 2):167S–70S. [PubMed]
27. Raji A, Williams GH, Jeunemaitre X, Hopkins PN, Hunt SC, Hollenberg NK, et al. Insulin resistance in hypertensives: effect of salt sensitivity, renin status and sodium intake. J Hypertens. 2001 Jan;19(1):99–105. [PubMed]
28. Williams JS, Williams GH, Jeunemaitre X, Hopkins PN, Conlin PR. Influence of dietary sodium on the renin-angiotensin-aldosterone system and prevalence of left ventricular hypertrophy by EKG criteria. J Hum Hypertens. 2005 Feb;19(2):133–8. [PubMed]
29. Price DA, Fisher ND, Lansang MC, Stevanovic R, Williams GH, Hollenberg NK. Renal perfusion in blacks: alterations caused by insuppressibility of intrarenal renin with salt. Hypertension. 2002 Aug;40(2):186–9. [PubMed]
30. Price DA, Fisher ND. The renin-angiotensin system in blacks: active, passive, or what? Curr Hypertens Rep. 2003 Jun;5(3):225–30. [PubMed]
31. Forman JP, Price DA, Stevanovic R, Fisher ND. Racial differences in renal vascular response to angiotensin blockade with captopril or candesartan. J Hypertens. 2007 Apr;25(4):877–82. [PubMed]
32. De’Oliveira JM, Price DA, Fisher ND, Allan DR, McKnight JA, Williams GH, et al. Autonomy of the renin system in type II diabetes mellitus: dietary sodium and renal hemodynamic responses to ACE inhibition. Kidney Int. 1997 Sep;52(3):771–7. [PubMed]
33. Price DA, De’Oliveira JM, Fisher ND, Williams GH, Hollenberg NK. The state and responsiveness of the renin-angiotensin-aldosterone system in patients with type II diabetes mellitus. Am J Hypertens. 1999 Apr;12(4 Pt 1):348–55. [PubMed]
34. Perlstein TS, Gerhard-Herman M, Hollenberg NK, Williams GH, Thomas A. Insulin induces renal vasodilation, increases plasma renin activity, and sensitizes the renal vasculature to angiotensin receptor blockade in healthy subjects. J Am Soc Nephrol. 2007 Mar;18(3):944–51. [PubMed]
35. Fisher ND, Hurwitz S, Ferri C, Jeunemaitre X, Hollenberg NK, Williams GH. Altered adrenal sensitivity to angiotensin II in low-renin essential hypertension. Hypertension. 1999 Sep;34(3):388–94. [PubMed]
36. Fisher ND, Gleason RE, Moore TJ, Williams GH, Hollenberg NK. Regulation of aldosterone secretion in hypertensive blacks. Hypertension. 1994 Feb;23(2):179–84. [PubMed]
37. Luft FC, Miller JZ, Grim CE, Fineberg NS, Christian JC, Daugherty SA, et al. Salt sensitivity and resistance of blood pressure. Age and race as factors in physiological responses. Hypertension. 1991 Jan;17(1 Suppl):I102–8. [PubMed]
38. Kojima S, Murakami K, Kimura G, Sanai T, Yoshida K, Imanishi M, et al. A gender difference in the association between salt sensitivity and family history of hypertension. Am J Hypertens. 1992 Jan;5(1):1–7. [PubMed]
39. Koolen MI, Bussemaker-Verduyn den Boer E, van Brummelen P. Clinical biochemical and haemodynamic correlates of sodium sensitivity in essential hypertension. J Hypertens Suppl. 1983 Dec;1(2):21–3. [PubMed]
40. Weinberger MH, Miller JZ, Luft FC, Grim CE, Fineberg NS. Definitions and characteristics of sodium sensitivity and blood pressure resistance. Hypertension. 1986 Jun;8(6 Pt 2):II127–34. [PubMed]
41. Ishibashi K, Oshima T, Matsuura H, Watanabe M, Ishida M, Ishida T, et al. Effects of age and sex on sodium chloride sensitivity: association with plasma renin activity. Clin Nephrol. 1994 Dec;42(6):376–80. [PubMed]
42. Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm BO, et al. Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system The Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Clin Chim Acta. 2010 May 29; [PubMed]
43. Doorenbos CR, van den Born J, Navis G, de Borst MH. Possible renoprotection by vitamin D in chronic renal disease: beyond mineral metabolism. Nat Rev Nephrol. 2009 Oct 27; [PubMed]
44. Pilz S, Tomaschitz A, Drechsler C, Dekker JM, Marz W. Vitamin D deficiency and myocardial diseases. Mol Nutr Food Res. 2010 Aug;54(8):1103–13. [PubMed]
45. Pilz S, Tomaschitz A, Ritz E, Pieber TR. Vitamin D status and arterial hypertension: a systematic review. Nat Rev Cardiol. 2009 Aug 18; [PubMed]
46. Forman JP, Giovannucci E, Holmes MD, Bischoff-Ferrari HA, Tworoger SS, Willett WC, et al. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007 May;49(5):1063–9. [PubMed]
47. Resnick LM. Ionic basis of hypertension, insulin resistance, vascular disease, and related disorders. The mechanism of “syndrome X” Am J Hypertens. 1993 Apr;6(4):123S–34S. [PubMed]
48. Gennari C, Nami R, Gonnelli S. Hypertension and primary hyperparathyroidism: the role of adrenergic and renin-angiotensin-aldosterone systems. Miner Electrolyte Metab. 1995;21(1–3):77–81. [PubMed]
49. Young EW, Morris CD, Holcomb S, McMillan G, McCarron DA. Regulation of parathyroid hormone and vitamin D in essential hypertension. Am J Hypertens. 1995 Oct;8(10 Pt 1):957–64. [PubMed]
50. Imaoka M, Morimoto S, Kitano S, Fukuo F, Ogihara T. Calcium metabolism in elderly hypertensive patients: possible participation of exaggerated sodium, calcium and phosphate excretion. Clin Exp Pharmacol Physiol. 1991 Sep;18(9):631–41. [PubMed]
51. Hulter HN, Melby JC, Peterson JC, Cooke CR. Chronic continuous PTH infusion results in hypertension in normal subjects. J Clin Hypertens. 1986 Dec;2(4):360–70. [PubMed]
52. Grant FD, Mandel SJ, Brown EM, Williams GH, Seely EW. Interrelationships between the renin-angiotensin-aldosterone and calcium homeostatic systems. J Clin Endocrinol Metab. 1992 Oct;75(4):988–92. [PubMed]
53. Fritsch S, Lindner V, Welsch S, Massfelder T, Grima M, Rothhut S, et al. Intravenous delivery of PTH/PTHrP type 1 receptor cDNA to rats decreases heart rate, blood pressure, renal tone, renin angiotensin system, and stress-induced cardiovascular responses. J Am Soc Nephrol. 2004 Oct;15(10):2588–600. [PubMed]
54. Hagstrom E, Hellman P, Larsson TE, Ingelsson E, Berglund L, Sundstrom J, et al. Plasma parathyroid hormone and the risk of cardiovascular mortality in the community. Circulation. 2009 Jun 2;119(21):2765–71. [PubMed]
55. Pilz S, Tomaschitz A, Drechsler C, Ritz E, Boehm BO, Grammer TB, et al. Parathyroid hormone level is associated with mortality and cardiovascular events in patients undergoing coronary angiography. Eur Heart J. 2010 Jul;31(13):1591–8. [PubMed]
56. Zhao G, Ford ES, Li C, Kris-Etherton PM, Etherton TD, Balluz LS. Independent associations of serum concentrations of 25-hydroxyvitamin D and parathyroid hormone with blood pressure among US adults. J Hypertens. 2010 Sep;28(9):1821–8. [PubMed]
57. Kong J, Qiao G, Zhang Z, Liu SQ, Li YC. Targeted vitamin D receptor expression in juxtaglomerular cells suppresses renin expression independent of parathyroid hormone and calcium. Kidney Int. 2008 Dec;74(12):1577–81. [PubMed]
58. Campbell DJ, Nussberger J, Stowasser M, Danser AH, Morganti A, Frandsen E, et al. Activity assays and immunoassays for plasma Renin and prorenin: information provided and precautions necessary for accurate measurement. Clin Chem. 2009 May;55(5):867–77. [PubMed]
59. Tomaschitz A, Pilz S. Aldosterone to renin ratio--a reliable screening tool for primary aldosteronism? Horm Metab Res. 2010 Jun;42(6):382–91. [PubMed]
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