Skip to main content
SpringerLink
Log in

The influence of alpha1-adrenergic blockade on the acute antihypertensive effect of nifedipine

  • Originals
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Summary

The hypotensive effect of vasodilator monotherapy in hypertension is attenuated by a baroreceptor-mediated increase in the sympathetic release of noradrenaline. Nifedipine induces a rise in noradrenaline release, but it is not known to affect noradrenaline-induced vascular contraction of smooth muscle to a clinically significant degree. The haemodynamic and hormonal effects of a single sublingual dose of nifedipine 20 mg in 8 moderately hypertensive patients have been studied before and during postsynaptic alpha1-blockade with prazosin. The antihypertensive effect of nifedipine was significantly increased by prazosin pretreatment (fall in mean arterial pressure 60 min after nifedipine: −16.7% with and −8.5% without prazosin), despite similar increases in plasma noradrenaline. Prazosin alone caused no change in supine blood pressure for 2 h after an oral dose of 2 mg. The findings are in keeping with the hypothesis that prazosin blocks a compensatory reaction to vasodilatation caused by nifedipine.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Braunwald E (1982) Mechanism of action of calcium-channel-blocking agents. N Engl J Med 307: 1618–27

    Google Scholar 

  2. Bolton TB (1979) Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev 59: 606–718

    Google Scholar 

  3. Leonetti G, Cuspidi C, Sampieri L, Terzoli L, Zanchetti A (1982) Comparison of cardiovascular, renal, and humoral effects of acute administration of two calcium channel blockers in normotensive and hypertensive subjects. J Cardiovasc Pharmacol 4: S 319–24

    Google Scholar 

  4. Van Zwieten PA, Timmermanns PBMWM (1983) Cardiovascular α2-receptors. J Mol Cell Cardiol 15: 713–33

    Google Scholar 

  5. McGrath JC (1982) Evidence for more than one type of postjunctional α-adrenoceptor. Biochem Pharmacol 31: 467–84

    Google Scholar 

  6. Kiowski W, Hulthen UL, Ritz R, Bühler FL (1983) α2-Adrenoceptor-mediated vasoconstriction of arteries. Clin Pharmacol Ther 34: 565–69

    Google Scholar 

  7. Elliott HL, Reid JL (1983) Evidence for postjunctional vascular α2-adrenoceptors in peripheral vascular regulation in man. Clin Sci 65: 237–41

    Google Scholar 

  8. Saeed M, Holtz J, Elsner D, Bassenge E (1983) Attenuation of sympathetic vasoconstriction by nifedipine: The role of vascular α2-adrenoceptors. Eur J Pharmacol 94: 149–53

    Google Scholar 

  9. Drayer JIM, Benraad ThJ (1975) The reliability of the measurement of plasma renin activity by radioimmunoassay. Clin Chim Acta 61: 309–24

    Google Scholar 

  10. De Man AJM, Hofman JA, Hendriks Th, Rosmalen FMA, Ross HA, Benraad ThJ (1980) A direct radio-immunoassay for plasma aldosterone: significance of endogenous cortisol. Neth J Med 23: 79–83

    Google Scholar 

  11. Hoffman JJML, Willemsen JJ, Thien Th, Benraad ThJ (1982) Radioenzymatic assay of plasma adrenaline and noradrenaline: evidence for a catechol-O-methyltransferase (COMT) inhibiting factor associated with essential hypertension. Clin Chim Acta 125: 319–27

    Google Scholar 

  12. Olivari MT, Bartorelli C, Polese A, Fiorentini C, Moruzzi P, Guazzi M (1979) Treatment of hypertension with nifedipine, a calcium antagonistic agent. Circulation 59: 1056–62

    Google Scholar 

  13. Huysmans FThM, Thien ThA, Sluiter HE, Koene RAP (1983) Acute treatment of hypertension with nifedipine. Neth J Med 26: 256–61

    Google Scholar 

  14. MacGregor GA, Rotellar C, Markandu ND, Smith SJ, Sagnella GA (1982) Contrasting effects of nifedipine, captopril, and propranolol in normotensive and hypertensive subjects. J Cardiovasc Pharmacol 4: S 358–62

    Google Scholar 

  15. Conen D, Bertel O, Dubach UC (1982) An oral calcium antagonist for treatment of hypertensive emergencies. J Cardiovasc Pharmacol 4: S 378–82

    Google Scholar 

  16. Murphy MB, Scriven AJ, Brown MJ, Causon R, Dollery CT (1982) The effects of nifedipine and hydralazine induced hypotension on sympathetic activity. Eur J Clin Pharmacol 23: 479–82

    Google Scholar 

  17. Lederballe Pedersen O, Mikkelsen E, Christensen NJ, Kornerup HJ, Pedersen EB (1979) Effect of nifedipine on plasma renin, aldosterone, and catecholamines in arterial hypertension. Eur J Clin Pharmacol 15: 235–40

    Google Scholar 

  18. Vierhapper H, Waldhäusl W (1982) Reduced pressor effect of angiotensin II and of noradrenaline in normal man following the oral administration of the calcium-antagonist nifedipine. Eur J Clin Invest 12: 263–67

    Google Scholar 

  19. Jee LD, Opie LH (1983) Acute hypotensive response to nifedipine added to prazosin in treatment of hypertension. Br Med J 287: 1514

    Google Scholar 

  20. Graham RM, Thornell IR, Gain JM, Bagnoli C, Oates HF, Stokes GS (1976) Prazosin: The first-dose phenomenon. Br Med J 2: 1293–94

    Google Scholar 

  21. McAreavey D, Cumming AMM, Sood VP, Lecki BJ, Morton JJ, Murray GD, Robertson JIS (1981) The effect of oral prazosin on blood pressure and plasma concentrations of renin and angiotensin II in man. Clin Sci 61: 457–605s

    Google Scholar 

  22. Larochelle P, Du Souich P, Hamet P, Laroque P, Armstrong J (1982) Prazosin plasma concentration and blood pressure reduction. Hypertension 4: 93–101

    Google Scholar 

  23. Pitterman AB, Rollins DE, Shen DD, Hurwitz A, Hassanein KM (1981) Alpha-adrenoceptor blockade with oral prazosin. Clin Pharmacol Ther 29: 143–48

    Google Scholar 

  24. Koch-Weser J (1974) Vasodilator drugs in the treatment of hypertension. Arch Intern Med 133: 1017–27

    Google Scholar 

  25. Sasso EH, O'Connor DT (1982) Prazosin depression of baroreflex function in hypertensive man. Eur J Clin Pharmacol 22: 7–14

    Google Scholar 

  26. Sluiter HE, Huysmans FThM, Thien ThA, van Lier HJJ, Koene RAP (1985) Haemodynamic, hormonal and diuretic effects of felodipine in healthy normotensive volunteers. Drugs 29 [Suppl 2]: 26–35

    Google Scholar 

  27. Thibonnier M, Bonnet M, Corvol P (1980) Antihypertensive effect of fractionated sublingual administration of nifedipine in moderate essential hypertension. Eur J Clin Pharmacol 17: 161–64

    Google Scholar 

  28. Schiffrin EL, Lis M, Gutkowska J, Genest J (1981) Role of Ca2+ in response of adrenal glomerulosa cells to angiotensin II, ACTH, K and ouabain. Am J Physiol 241: E42–46

    Google Scholar 

  29. Fakunding JL, Catt KJ (1980) Dependence of aldosterone stimulation in adrenal glomerulosa cells on calcium uptake: Effects of lanthanum and verapamil. Endocrinology 107: 1345–53

    Google Scholar 

  30. Millar JA, McLean K, Reid JL (1981) Calcium antagonists decrease adrenal and vascular responsiveness to angiotensin II in normal man. Clin Sci 61: 65–68S

    Google Scholar 

  31. Klütsch K, Schmidt P, Grosswendt J (1972) Der Einfluß von Bay a 1040 auf die Nierenfunktion des Hypertonikers. Arzneimittelforsch (Drug Res) 22: 377–80

    Google Scholar 

  32. Guyton AC, Coleman TG, Cowley AW Jr, Manning RD Jr, Norman RA Jr, Ferguson JD (1974) A systems analysis approach to understanding long-range arterial blood pressure control and hytension. Circ Res 35: 159–76

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Nephrology, University of Nijmegen, The Netherlands

    H. E. Sluiter, F. Th. M. Huysmans & R. A. P. Koene

  2. General Internal Medicine, Sint Radboud Ziekenhuis, University of Nijmegen, The Netherlands

    Th. A. Thien

Authors
  1. H. E. Sluiter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Th. M. Huysmans
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Th. A. Thien
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. A. P. Koene
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sluiter, H.E., Huysmans, F.T.M., Thien, T.A. et al. The influence of alpha1-adrenergic blockade on the acute antihypertensive effect of nifedipine. Eur J Clin Pharmacol 29, 263–267 (1985). https://doi.org/10.1007/BF00544078

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00544078

Key words

Search

Navigation