Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

The effect of the calcium antagonist nifedipine on pressor and aldosterone responses to angiotensin II in normal man

  • 35 Accesses

  • 78 Citations


The effects of the calcium entry blocker nifedipine on blood pressure (BP) and the pressor and aldosterone responses to graded infusions of angiotensin II were studied in normal subjects using 3 protocols. Study 1 was a randomised double-blind placebo-controlled trial of nifedipine (20 mg p.o.) on supine and erect BP in 9 subjects. There was a highly significant fall in BP: (8±4 mmHg; mean±SDM;p<0.001) with maximum changes occurring 30 min after drug administration. Significant reciprocal changes in pulse rate were observed. These changes were not altered by prior administration of the prostaglandin synthetase inhibitor flurbiprofen (100 mg). In Study 2, 6 subjects were given nifedipine (20 mg) or no treatment mid-way between 2 identical graded infusions of angiotensin II (5, 10 and 20 ng/kg/min) separated by an interval of 1 h on each of 2 study days, and blood pressure and aldosterone responses were measured. There was a significant attenuation of both pressor (p<0.05) and aldosterone (p<0.05) responses. The changes in aldosterone responses were not due to changes in plasma renin, potassium or adrenocorticotrophin. In study 3 the pressor and aldosterone responses to angiotensin II (2, 5, 10 and 20 ng/kg/min) were studied after 3 days treatment with nifedipine (20 mg thrice daily) or placebo. Pressor dose response curves to both angiotensin II and noradrenaline were shifted in parallel to the right, but not significantly, and aldosterone responses to angiotensin II were unchanged by nifedipine. These results show that nifedipine may decrease BP in normal subjects by decreasing pressor and aldosterone responses to angiotensin II and that the aldosterone response to angiotensin II in man is possibly calcium-dependent.

This is a preview of subscription content, log in to check access.


  1. Altura BM, Altura BJ (1976) Vascular smooth muscle and prostaglandins. Fed Proc 35: 2360–2366

  2. d'Auriac AG, Baudouin M, Meyer P (1972) Mechanism of action of angiotensin in the smooth muscle cell. Circ Res [Suppl 2] 30: 151–157

  3. De Champlain J, Genest J, Veyrat R, Boucher R (1966) Factors controlling renin in man. Arch Intern Med 117: 355–363

  4. De Man AJM, Hofman JA, Hendricks T, Rosmalen FMA, Ross HA, Benraad TJ (1980) A direct radioimmunoassay for plasma aldosterone: significance of endogenous cortisol. Neth J Med 23: 79–83

  5. Barbarino A, de Marinis L (1980) Calcium antagonists and hormone release II. Effects of verapamil on basal, gonadotrophin-releasing hormone and thyrotrophin-releasing hormone-induced pituitary hormone release in normal subjects. J Clin Endocrinol Metab 51: 749–753

  6. Berl T, Raz A, Wald H, Horowitz J, Czackes W (1977) Prostaglandin synthesis inhibition and the action of vasopressin: studies in man and rat. Am J Physiol 232: F529-F537

  7. Bianchetti MG, Beretta-Piccoli C, Wiedmann P, Boehringer K, Link L, Morton JJ (1982) Studies on aldosterone responsiveness to angiotensin II during clinical variations in calcium metabolism in normal man. Clin Sci (in press)

  8. Chiu T, Freer RJ (1979) Angiotensin-induced steroidogenesis in rabbit adrenal: effects of pH and calcium. Mol Cell Endocrinol 13: 159–166

  9. Dluhy RG, Axelrod L, Underwood RH, Williams GH (1972) Studies on the control of aldosterone concentration in normal man. II: Effect of dietary potassium and acute potassium infusion. J Clin Invest 51: 1950–1957

  10. Fakunding JL, Catt KJ (1980) Dependence of aldosterone stimulation in adrenal glomerulosa cells on calcium uptake: effects of lanthanum and verapamil. Endocrinology 107: 1345–1353

  11. Fakunding JL, Chow R, Catt KJ (1979) The role of calcium in the stimulation of aldosterone production by adrenocorticotrophin, angiotensin II and potassium in isolated glomerulosa cells. Endocrinology 105: 327–333

  12. Fleckenstein A (1976) Nifedipine: basic pharmacological mechanism and therapeutic efficiency. Proceedings 3rd Adalat Symposium, Jatene AD, Lichtlen PR (ed) Excerpta Med, Amsterdam, pp 1–13

  13. Godfraind T, Miller RC (1982) Actions of prostaglandin F and noradrenaline on calcium exchange and contraction in rat mesenteric arteries and their sensitivity to calcium entry blockers. Br J Pharmacol 75: 229–236

  14. Henry DP, Starman BJ, Johnson DG, Williams RH (1975) A sensitive radioenzymatic assay for norepinephrine in tissues and plasma. Life Sci 16: 375–384

  15. Kondo S, Kuchiki A, Yamamoto K, Akimoto K, Takahashi K, Awatea N, Singimoto I (1980) Identification of nifedipine metabolites and their determination by gas chromatography. Clin Pharm Bull 28: 1–7

  16. Kramer HJ, Dusing R, Stinnesbeck B, Prior W, Backer A, Eden J, Kipnowski J, Glanzer K, Kruck F (1980) Interaction of conventional and antikaliuretic diuretics with the renal prostaglandin system. Clin Sci 59: 67–70

  17. Lederballe-Pederson O, Christensen NJ, Ramsch KD (1980) Comparison of nifedipine in normotensive and hypertensive man. J Cardiovasc Pharmacol 2: 357–366

  18. Lederballe-Pederson O, Mikkelsen E, Christensen NJ, Kornerup HJ, Pederson EB (1979) Effects of nifedipine on plasma renin, aldosterone and catecholamines in arterial hypertension. Eur J Clin Pharmacol 15: 235–240

  19. Levy JV (1973) Papaverine antagonism of prostaglandin E2-induced contraction of rabbit aortic strips. Res Commun Chem Pathol Pharmacol 5: 297–310

  20. Levy JV (1980) Prostaglandin-induced contraction of isolated aortic strips from normal and spontaneously hypertensive rats. (SHR) Prostaglandins 19: 517–525

  21. Lin T, Murono E, Osterman J, Troen P, Nankin HR (1979) The effects of verapamil on interstitial cell steroidogenesis. Int J Andrology 2: 549–558

  22. Mason P, Fraser R (1975) Estimation of aldosterone, 11-deoxycorticosterone, 18-hydroxy-11-deoxycorticosterone, corticosterone, cortisol and 11-deoxycortisol in human plasma by gasliquid chromatography with electron capture detection. J Endocrinol 64: 277–288

  23. Millar JA, Leckie BJ, Semple PF, Morton JJ, Sonkodi S, Robertson JIS (1978) Active and inactive renin in human plasma: renal arteriovenous differences and relationship with angiotensin and renin-substrate. Circ Res [Suppl 1] 43: 120–127

  24. Millar JA, Struthers AD (1981) Effect of nifedipine on bronchomotor tone and histamine reactivity in asthma. Br Med J 283: 796

  25. Millar JA, Struthers AD, Beastall GH, Reid JL (1982) Effect of nifedipine on blood pressure and adrenocortical responses to trophic stimuli in man. J Cardiovasc Pharmacol (in press)

  26. Olivari MT, Bartorelli C, Polese A, Fiorentini C, Murozzi P, Guazzi MD (1979) Treatment of hypertension with nifedipine, a calcium antagonist agent. Circulation 59: 1056–1062

  27. Semple PF, Buckingham JC, Mason PA, Fraser R (1979) Suppression of plasma ACTH concentration by angiotensin II infusion in normal humans and in a subject with a steroid 17α-hydroxylase defect. Clin Endocrinol 10: 137–144

  28. Shima S, Kawashima Y, Harai M (1978) Studies on cyclic nucleotides in the adrenal gland VIII. Effects of angiotensin on adenosine 3′-5′-monophosphate and steroidogenesis in the adrenal cortex. Endocrinology 103: 1361–1367

  29. Skinner SL (1967) Improved methods for renin ‘concentration’ and ‘activity’ in human plasma. Methods using selective denaturation of renin substrate. Circ Res 20: 392–402

  30. Sumner DJ, Elliott HL, Reid JL (1982) The analysis of pressor dose-response curves in human subjects. Clin Pharmacol Ther (in press)

  31. Wheeler ES, Weiss GB (1980) Effects of prostaglandin E on contractility and45Ca release in rabbit aortic smooth muscle. Prostaglandins 19: 761–778

  32. Williams DO, Barnes PJ, Vickers HP, Rudolf M (1981) Effect of nifedipine on bronchomotor tone and histamine reactivity in asthma. Br Med J 283: 796

  33. Williams BC, MacDougall JG, Tait JF, Tait SAS (1981) Calcium efflux and steroid output from superfused rat adrenal cells; effects of potassium, adrenocorticotrophin hormone, 5-hydroxytryptamine, adenosine-3′5′-cyclic monophosphate and angiotensin I and II. Clin Sci 61: 541–551

Download references

Author information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Millar, J.A., McLean, K.A., Sumner, D.J. et al. The effect of the calcium antagonist nifedipine on pressor and aldosterone responses to angiotensin II in normal man. Eur J Clin Pharmacol 24, 315–321 (1983). https://doi.org/10.1007/BF00610047

Download citation

Key words

  • aldosterone
  • flurbiprofen
  • nifedipine
  • blood pressure
  • calcium flux
  • prostaglandins