• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Aug 1986; 78(2): 366–374.
PMCID: PMC423555

Baroreflex control of plasma norepinephrine and heart period in healthy subjects and diabetic patients.

Abstract

Resting diabetic patients may have excessively rapid heart rates, reduced heart rate variability, and subnormal plasma catecholamine levels. Although all of these abnormalities may relate in some way to baroreceptor reflex function, there have been surprisingly few attempts to evaluate systematically baroreflex mechanisms in diabetic patients. Accordingly, we studied autonomic responses over a range of pharmacologically induced arterial pressure changes in 10 unselected young adult insulin-dependent diabetic patients who had no symptoms of autonomic neuropathy, and 12 age-matched nondiabetic subjects. Sympathetic responses were estimated from antecubital vein plasma norepinephrine levels, and parasympathetic responses were estimated from electrocardiographic R-R intervals and their variability (standard deviation). Both were correlated with other noninvasive indexes of peripheral and central nervous system function. Multiple derangements of baroreflex function were found in the diabetic patients studied. Sympathetic abnormalities included subnormal baseline norepinephrine levels, virtual absence of changes of norepinephrine levels during changes of arterial pressure, and supranormal pressor responses to phenylephrine infusions. Parasympathetic abnormalities included subnormal baseline standard deviations of R-R intervals, and R-R interval prolongations during elevations of arterial pressure which were unmistakably present, but subnormal. Our data suggest that in diabetic patients, subnormal baseline plasma norepinephrine levels may signify profound, possibly structural defects of sympathetic pathways. Subnormal resting levels of respiratory sinus arrhythmia may have different implications, however, since vagal, unlike sympathetic reflex abnormalities, can be reversed partly by arterial pressure elevations.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Murray A, Ewing DJ, Campbell IW, Neilson JM, Clarke BF. RR interval variations in young male diabetics. Br Heart J. 1975 Aug;37(8):882–885. [PMC free article] [PubMed]
  • Young RJ, Ewing DJ, Clarke BF. Nerve function and metabolic control in teenage diabetics. Diabetes. 1983 Feb;32(2):142–147. [PubMed]
  • Hilsted J, Galbo H, Christensen NJ. Impaired responses of catecholamines, growth hormone, and cortisol to graded exercise in diabetic autonomic neuropathy. Diabetes. 1980 Apr;29(4):257–262. [PubMed]
  • Watkins PJ, Mackay JD. Cardiac denervation in diabetic neuropathy. Ann Intern Med. 1980 Feb;92(2 Pt 2):304–307. [PubMed]
  • Bennett T, Hosking DJ, Hampton JR. Baroreflex sensitivity and responses to the Valsalva manoeuvre in subjects with diabetes mellitus. J Neurol Neurosurg Psychiatry. 1976 Feb;39(2):178–183. [PMC free article] [PubMed]
  • Bennett T, Hosking DJ, Hampton JR. Cardiovascular responses to graded reductions of central blood volume in normal subjects and in patients with diabetes mellitus. Clin Sci (Lond) 1980 Mar;58(3):193–200. [PubMed]
  • Christensen NJ. Plasma catecholamines in long-term diabetics with and without neuropathy and in hypophysectomized subjects. J Clin Invest. 1972 Apr;51(4):779–787. [PMC free article] [PubMed]
  • Fagius J, Wallin BG. Sympathetic reflex latencies and conduction velocities in patients with polyneuropathy. J Neurol Sci. 1980 Sep;47(3):449–461. [PubMed]
  • Low PA, Walsh JC, Huang CY, McLeod JG. The sympathetic nervous system in diabetic neuropathy. A clinical and pathological study. Brain. 1975 Sep;98(3):341–356. [PubMed]
  • Bennett T, Farquhar IK, Hosking DJ, Hampton JR. Assessment of methods for estimating autonomic nervous control of the heart in patients with diabetes mellitus. Diabetes. 1978 Dec;27(12):1167–1174. [PubMed]
  • Bennett T, Fentem PH, Fitton D, Hampton JR, Hosking DJ, Riggott PA. Assessment of vagal control of the heart in diabetes. Measures of R-R interval variation under different conditions. Br Heart J. 1977 Jan;39(1):25–28. [PMC free article] [PubMed]
  • Ewing DJ, Borsey DQ, Bellavere F, Clarke BF. Cardiac autonomic neuropathy in diabetes: comparison of measures of R-R interval variation. Diabetologia. 1981 Jul;21(1):18–24. [PubMed]
  • Goldstein DS, McCarty R, Polinsky RJ, Kopin IJ. Relationship between plasma norepinephrine and sympathetic neural activity. Hypertension. 1983 Jul-Aug;5(4):552–559. [PubMed]
  • Grossman SH, Davis D, Gunnells JC, Shand DG. Plasma norepinephrine in the evaluation of baroreceptor function in humans. Hypertension. 1982 Jul-Aug;4(4):566–571. [PubMed]
  • Eckberg DL. Human sinus arrhythmia as an index of vagal cardiac outflow. J Appl Physiol Respir Environ Exerc Physiol. 1983 Apr;54(4):961–966. [PubMed]
  • Katona PG, Jih F. Respiratory sinus arrhythmia: noninvasive measure of parasympathetic cardiac control. J Appl Physiol. 1975 Nov;39(5):801–805. [PubMed]
  • Hjemdahl P, Daleskog M, Kahan T. Determination of plasma catecholamines by high performance liquid chromatography with electrochemical detection: comparison with a radioenzymatic method. Life Sci. 1979 Jul 9;25(2):131–138. [PubMed]
  • Miller ED, Jr, Beckman JJ, Woodside JR, Jr, Althaus MS, Peach MJ. Blood pressure control during anesthesia: importance of the peripheral sympathetic nervous system and renin. Anesthesiology. 1983 Jan;58(1):32–37. [PubMed]
  • Abraham EC, Huff TA, Cope ND, Wilson JB, Jr, Bransome ED, Jr, Huisman TH. Determination of the glycosylated hemoglobins (HB AI) with a new microcolumn procedure. Suitability of the technique for assessing the clinical management of diabetes mellitus. Diabetes. 1978 Sep;27(9):931–937. [PubMed]
  • Allison T, Wood CC, Goff WR. Brain stem auditory, pattern-reversal visual, and short-latency somatosensory evoked potentials: latencies in relation to age, sex, and brain and body size. Electroencephalogr Clin Neurophysiol. 1983 Jun;55(6):619–636. [PubMed]
  • Sundlöf G, Wallin BG. Human muscle nerve sympathetic activity at rest. Relationship to blood pressure and age. J Physiol. 1978 Jan;274:621–637. [PMC free article] [PubMed]
  • Fouad FM, Tarazi RC, Ferrario CM, Fighaly S, Alicandri C. Assessment of parasympathetic control of heart rate by a noninvasive method. Am J Physiol. 1984 Jun;246(6 Pt 2):H838–H842. [PubMed]
  • Wallin BG, Sundlöf G, Eriksson BM, Dominiak P, Grobecker H, Lindblad LE. Plasma noradrenaline correlates to sympathetic muscle nerve activity in normotensive man. Acta Physiol Scand. 1981 Jan;111(1):69–73. [PubMed]
  • Robertson D, Johnson GA, Robertson RM, Nies AS, Shand DG, Oates JA. Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man. Circulation. 1979 Apr;59(4):637–643. [PubMed]
  • Oberg B, Thorén P. Increased activity in left ventricular receptors during hemorrhage or occlusion of caval veins in the cat. A possible cause of the vaso-vagal reaction. Acta Physiol Scand. 1972 Jun;85(2):164–173. [PubMed]
  • Murray RH, Thompson LJ, Bowers JA, Albright CD. Hemodynamic effects of graded hypovolemia and vasodepressor syncope induced by lower body negative pressure. Am Heart J. 1968 Dec;76(6):799–811. [PubMed]
  • Wallin BG, Sundlöf G. Sympathetic outflow to muscles during vasovagal syncope. J Auton Nerv Syst. 1982 Nov;6(3):287–291. [PubMed]
  • Chen RY, Matteo RS, Fan FC, Schuessler GB, Chien S. Resetting of baroreflex sensitivity after induced hypotension. Anesthesiology. 1982 Jan;56(1):29–35. [PubMed]
  • Lin MS, McNay JL, Shepherd AM, Keeton TK. Effects of hydralazine and sodium nitroprusside on plasma catecholamines and heart rate. Clin Pharmacol Ther. 1983 Oct;34(4):474–480. [PubMed]
  • Dorward PK, Riedel W, Burke SL, Gipps J, Korner PI. The renal sympathetic baroreflex in the rabbit. Arterial and cardiac baroreceptor influences, resetting, and effect of anesthesia. Circ Res. 1985 Oct;57(4):618–633. [PubMed]
  • Clarke BF, Ewing DJ, Campbell IW. Diabetic autonomic neuropathy. Diabetologia. 1979 Oct;17(4):195–212. [PubMed]
  • Grubeck-Loebenstein B, Vierhapper H, Waldhäusl W, Korn A, Graf M, Panzer S. Adrenergic mechanisms and blood pressure regulation in diabetes mellitus. Klin Wochenschr. 1982 Aug 16;60(16):823–828. [PubMed]
  • Lake CR, Chernow B, Goldstein DS, Glass DG, Coleman M, Ziegler MG. Plasma catecholamine levels in normal subjects and in patients with secondary hypertension. Fed Proc. 1984 Jan;43(1):52–56. [PubMed]
  • Cryer PE, Silverberg AB, Santiago JV, Shah SD. Plasma catecholamines in diabetes. The syndromes of hypoadrenergic and hyperadrenergic postural hypotension. Am J Med. 1978 Mar;64(3):407–416. [PubMed]
  • Neubauer B, Christensen NJ. Norepinephrine, epinephrine, and dopamine contents of the cardiovascular system in long-term diabetics. Diabetes. 1976 Jan;25(1):6–10. [PubMed]
  • Goldstein DS. Arterial baroreflex sensitivity, plasma catecholamines, and pressor responsiveness in essential hypertension. Circulation. 1983 Aug;68(2):234–240. [PubMed]
  • Christlieb AR, Janka HU, Kraus B, Gleason RE, Icasas-Cabral EA, Aiello LM, Cabral BV, Solano A. Vascular reactivity to angiotensin II and to norepinephrine in diabetic subjects. Diabetes. 1976 Apr;25(4):268–274. [PubMed]
  • Kontos HA, Richardson DW, Norvell JE. Norepinephrine depletion in idiopathic orthostatic hypotension. Ann Intern Med. 1975 Mar;82(3):336–341. [PubMed]
  • Ziegler MG, Lake CR, Kopin IJ. The sympathetic-nervous-system defect in primary orthostatic hypotension. N Engl J Med. 1977 Feb 10;296(6):293–297. [PubMed]
  • Donald MW, Erdahl DL, Surridge DH, Monga TN, Lawson JS, Bird CE, Letemendia FJ. Functional correlates of reduced central conduction velocity in diabetic subjects. Diabetes. 1984 Jul;33(7):627–633. [PubMed]
  • Duchen LW, Anjorin A, Watkins PJ, Mackay JD. Pathology of autonomic neuropathy in diabetes mellitus. Ann Intern Med. 1980 Feb;92(2 Pt 2):301–303. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • Compound
    Compound
    PubChem Compound links
  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...