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J Clin Invest. Apr 1985; 75(4): 1285–1290.
PMCID: PMC425457

Correction of abnormal renal blood flow response to angiotensin II by converting enzyme inhibition in essential hypertensives.


In 40-50% of patients with essential hypertension, a high sodium intake does not increase renal blood flow (RBF). These patients have been defined as nonmodulators because sodium intake does not modulate renal and adrenal responsiveness to angiotensin II (AII). To define the role of AII in mediating this altered responsiveness, we assessed the effect of a converting enzyme inhibitor (enalapril) on RBF and its responsiveness to AII in 25 patients with essential hypertension--10 modulators and 15 nonmodulators--and 9 normotensive controls. After 5 d of a 200-meq sodium intake, the nonmodulators did not increase RBF, whereas the normotensives (79 +/- 28 ml/min per 1.73 m2) and modulators (75 +/- 26 ml/min per 1.73 m2) did (P less than 0.025). Arterial blood pressure did not change in the modulators with the salt loading, whereas in the nonmodulators, blood pressure rose (P less than 0.004). After enalapril administration for 66 h, there was a significant difference (P less than 0.01, Fisher Exact Test) in the blood pressure response in the two hypertensive subgroups. In the modulators, there was no change; in the nonmodulators, despite the high salt diet, a blood pressure reduction occurred. In parallel, basal RBF and RBF responsiveness to AII were not changed after converting enzyme inhibition in the normotensive control (n = 9) or the hypertensive modulators (n = 10). Conversely, in the nonmodulators (n = 14), the basal RBF increased significantly (83 +/- 25 ml/min per 1.73 m2; P = 0.01), the increment being indistinguishable from the response to salt loading in normal subjects. Furthermore, renovascular responsiveness to infused AII was also significantly enhanced (P = 0.027) in the nonmodulators, suggesting that enalapril-induced increase in RBF reflected a fall in intrarenal AII levels, and not an increase in prostaglandins or kinins, which would have blunted the renal response to AII. Thus, short-term converting enzyme inhibition corrected abnormalities in sodium-mediated modulation of renal vascular responsiveness to AII. The close quantitative relation of the increase in RBF with sodium loading in normal subjects and modulators, and with converting enzyme inhibition in nonmodulators, viewed in the context of the effectiveness of enalapril only in the latter, and parallel shifts in sensitivity to AII, raises the intriguing possibility that converting enzyme inhibition reversed the failure of the renal blood supply to respond to sodium loading. Thus, converting enzyme inhibitors may reduce blood pressure specifically in this subset of patients with essential hypertension, who are sodium sensitive by way of mechanisms more closely related to local than systemic activity of the renin-angiotensin system.

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Selected References

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  • Shoback DM, Williams GH, Moore TJ, Dluhy RG, Podolsky S, Hollenberg NK. Defect in the sodium-modulated tissue responsiveness to angiotensin II in essential hypertension. J Clin Invest. 1983 Dec;72(6):2115–2124. [PMC free article] [PubMed]
  • Williams GH, Tuck ML, Sullivan JM, Dluhy RG, Hollenberg NK. Parallel adrenal and renal abnormalities in young patients with essential hypertension. Am J Med. 1982 Jun;72(6):907–914. [PubMed]
  • Moore TJ, Williams GH, Dluhy RG, Bavli SZ, Himathongkam T, Greenfield M. Altered renin-angiotensin-aldosterone relationships in normal renin essential hypertension. Circ Res. 1977 Aug;41(2):167–171. [PubMed]
  • Dluhy RG, Bavli SZ, Leung FK, Solomon HS, Moore TJ, Hollenberg NK, Williams GH. Abnormal adrenal responsiveness and angiotensin II dependency in high renin essential hypertension. J Clin Invest. 1979 Nov;64(5):1270–1276. [PMC free article] [PubMed]
  • Taylor T, Moore TJ, Hollenberg NK, Williams GH. Converting-enzyme inhibition corrects the altered adrenal response to angiotensin II in essential hypertension. Hypertension. 1984 Jan-Feb;6(1):92–99. [PubMed]
  • Shoback DM, Williams GH, Hollenberg NK, Davies RO, Moore TJ, Dluhy RG. Endogenous angiotensin II as a determinant of sodium-modulated changes in tissue responsiveness to angiotensin II in normal man. J Clin Endocrinol Metab. 1983 Oct;57(4):764–770. [PubMed]
  • Tuck ML, Dluhy RG, Williams GH. A specific role for saline or the sodium ion in the regulation of renin and aldosterone secretion. J Clin Invest. 1974 Apr;53(4):988–995. [PMC free article] [PubMed]
  • Schnurr E, Lahme W, Küppers H. Measurement of renal clearance of inulin and PAH in the steady state without urine collection. Clin Nephrol. 1980 Jan;13(1):26–29. [PubMed]
  • Emanuel RL, Cain JP, Williams GH. Double antibody radioimmunoassay of renin activity and angiotensin II in human peripheral plasma. J Lab Clin Med. 1973 Apr;81(4):632–640. [PubMed]
  • Underwood RH, Williams GH. The simultaneous measurement of aldosterone, cortisol, and corticosterone in human peripheral plasma by displacement analysis. J Lab Clin Med. 1972 May;79(5):848–862. [PubMed]
  • Sawyer WH, Blair-West JR, Simpson PA, Sawyer MK. Renal responses of Australian lungfish to vasotocin, angiotensin II, and NaCl infusion. Am J Physiol. 1976 Aug;231(2):593–602. [PubMed]
  • Hollenberg NK, Chenitz WR, Adams DF, Williams GH. Reciprocal influence of salt intake on adrenal glomerulosa and renal vascular responses to angiotensin II in normal man. J Clin Invest. 1974 Jul;54(1):34–42. [PMC free article] [PubMed]
  • Gunther S, Gimbrone MA, Jr, Alexander RW. Regulation by angiotensin II of its receptors in resistance blood vessels. Nature. 1980 Sep 18;287(5779):230–232. [PubMed]
  • Kimbrough HM, Jr, Vaughan ED, Jr, Carey RM, Ayers CR. Effect of intrarenal angiotensin II blockade on renal function in conscious dogs. Circ Res. 1977 Feb;40(2):174–178. [PubMed]
  • Hollenberg NK, Meggs LG, Williams GH, Katz J, Garnic JD, Harrington DP. Sodium intake and renal responses to captopril in normal man and in essential hypertension. Kidney Int. 1981 Aug;20(2):240–245. [PubMed]
  • Hollenberg NK, Williams GH. Volume control and altered renal and adrenal responsiveness to angiotensin in essential hypertension: implications for treatment with converting enzyme inhibition. J Hypertens Suppl. 1983 Oct;1(1):119–128. [PubMed]
  • Williams GH, Hollenberg NK. Accentuated vascular and endocrine response to SQ 20881 in hypertension. N Engl J Med. 1977 Jul 28;297(4):184–188. [PubMed]
  • Mimran A, Targhetta R, Laroche B. The antihypertensive effect of captopril. Evidence for an influence of kinins. Hypertension. 1980 Nov-Dec;2(6):732–737. [PubMed]
  • Swartz SL, Williams GH, Hollenberg NK, Levine L, Dluhy RG, Moore TJ. Captopril-induced changes in prostaglandin production: relationship to vascular responses in normal man. J Clin Invest. 1980 Jun;65(6):1257–1264. [PMC free article] [PubMed]
  • Moore TJ, Crantz FR, Hollenberg NK, Koletsky RJ, Leboff MS, Swartz SL, Levine L, Podolsky S, Dluhy RG, Williams GH. Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension. Hypertension. 1981 Mar-Apr;3(2):168–173. [PubMed]
  • Hollenberg NK, Epstein M, Guttmann RD, Conroy M, Basch RI, Merrill JP. Effect of sodium balance on intrarenal distribution of blood flow in normal man. J Appl Physiol. 1970 Mar;28(3):312–317. [PubMed]
  • Hollenberg NK, Adams DF, Solomon HS, Rashid A, Abrams HL, Merrill JP. Senescence and the renal vasculature in normal man. Circ Res. 1974 Mar;34(3):309–316. [PubMed]
  • Laragh JH. Vasoconstriction-volume analysis for understanding and treating hypertension: the use of renin and aldosterone profiles. Am J Med. 1973 Sep;55(3):261–274. [PubMed]
  • Case DB, Wallace JM, Keim HJ, Weber MA, Sealey JE, Laragh JH. Possible role of renin in hypertension as suggested by renin-sodium profiling and inhibition of converting enzyme. N Engl J Med. 1977 Mar 24;296(12):641–646. [PubMed]
  • Brunner HR, Gavras H, Waeber B, Kershaw GR, Turini GA, Vukovich RA, McKinstry DN, Gavras I. Oral angiotensin-converting enzyme inhibitor in long-term treatment of hypertensive patients. Ann Intern Med. 1979 Jan;90(1):19–23. [PubMed]
  • Johnston CI, Millar JA, McGrath BP, Matthews PG. Long-term effects of captopril (SQ14 225) on blood-pressure and hormone levels in essential hypertension. Lancet. 1979 Sep 8;2(8141):493–496. [PubMed]
  • Swartz SL, Williams GH, Hollenberg NK, Crantz FR, Moore TJ, Levine L, Sasahara AA, Dluhy RG. Endocrine profile in the long-term phase of converting-enzyme inhibition. Clin Pharmacol Ther. 1980 Oct;28(4):499–508. [PubMed]

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