Skip to main content
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1987 Oct;24(4):465–472. doi: 10.1111/j.1365-2125.1987.tb03199.x

Converting-enzyme inhibition buffers the counter-regulatory response to acute administration of nicardipine.

M Bellet 1, P Sassano 1, T Guyenne 1, P Corvol 1, J Menard 1
PMCID: PMC1386308  PMID: 3689627

Abstract

1. To investigate the interaction of angiotensin-converting-enzyme (ACE) inhibitor and calcium antagonist, we conducted a double-blind randomized, placebo-controlled crossover study of a new ACE inhibitor (CGS 14824 A, 20 mg) during intravenous administration (i.v.) of nicardipine in eight normotensive healthy subjects. Nicardipine was infused to give cumulative doses of 1.25, 3.75, and 8.75 mg after 10, 20 and 30 min. 2. ACE inhibition was demonstrated 24 h after the first CGS 14 824 A intake (61%). Three hours after the second dose this inhibition was more marked (98%). 3. I.v. nicardipine administration induced a significant and similar fall in systolic or diastolic blood pressure with and without ACE activity (-3/-6 vs -2/-8%), while tachycardia was significantly decreased by CGS 14 824 A (+14 vs +30%, P less than 0.02). The increase of plasma noradrenaline was also significantly blunted (+1.8 +/- 0.3 vs +3.1 +/- 0.7 pmol ml-1, P less than 0.05). 4. Active and total plasma renin increased at the end of nicardipine infusion in the presence or absence of ACE inhibition. Inactive renin did not increase after nicardipine infusion under placebo. It was higher 3 h after the second intake of CGS 14 824 A and then increased after nicardipine infusion. 5. The rise in plasma aldosterone during i.v. calcium antagonist infusion was diminished after ACE inhibition (126 +/- 39 vs 277 +/- 120 pmol l-1, P less than 0.02). 6. In conclusion, converting-enzyme inhibition buffers the rise in heart rate, plasma noradrenaline and plasma aldosterone induced by acute calcium blockade.

Full text

PDF
465

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ajayi A. A., Lees K. R., Reid J. L. Effects of angiotensin converting enzyme inhibitor, perindopril, on autonomic reflexes. Eur J Clin Pharmacol. 1986;30(2):177–182. doi: 10.1007/BF00614298. [DOI] [PubMed] [Google Scholar]
  2. Ajayi A. A., Reid J. L. The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects. Br J Clin Pharmacol. 1986 Mar;21(3):338–339. doi: 10.1111/j.1365-2125.1986.tb05203.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Becker R. H., Struthers A. D., Brown M. J. Effect of captopril on changes in plasma noradrenaline induced by sodium nitroprusside. Br J Clin Pharmacol. 1986 Oct;22(4):409–413. doi: 10.1111/j.1365-2125.1986.tb02910.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brunner H. R., Nussberger J., Waeber B. Effects of angiotensin converting enzyme inhibition: a clinical point of view. J Cardiovasc Pharmacol. 1985;7 (Suppl 4):S73–S81. doi: 10.1097/00005344-198507004-00015. [DOI] [PubMed] [Google Scholar]
  5. Clementi W. A., Durst N. L., McNay J. L., Keeton T. K. Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients. Hypertension. 1986 Mar;8(3):229–237. doi: 10.1161/01.hyp.8.3.229. [DOI] [PubMed] [Google Scholar]
  6. Cody R. J., Franklin K. W., Kluger J., Laragh J. H. Sympathetic responsiveness and plasma norepinephrine during therapy of chronic congestive heart failure with captopril. Am J Med. 1982 May;72(5):791–797. doi: 10.1016/0002-9343(82)90547-2. [DOI] [PubMed] [Google Scholar]
  7. Giudicelli J. F., Berdeaux A., Edouard A., Richer C., Jacolot D. The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects. Br J Clin Pharmacol. 1985 Sep;20(3):211–218. doi: 10.1111/j.1365-2125.1985.tb05063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Guazzi M. D., De Cesare N., Galli C., Salvioni A., Tramontana C., Tamborini G., Bartorelli A. Calcium-channel blockade with nifedipine and angiotensin converting-enzyme inhibition with captopril in the therapy of patients with severe primary hypertension. Circulation. 1984 Aug;70(2):279–284. doi: 10.1161/01.cir.70.2.279. [DOI] [PubMed] [Google Scholar]
  9. Heesch C. M., Miller B. M., Thames M. D., Abboud F. M. Effects of calcium channel blockers on isolated carotid baroreceptors and baroreflex. Am J Physiol. 1983 Oct;245(4):H653–H661. doi: 10.1152/ajpheart.1983.245.4.H653. [DOI] [PubMed] [Google Scholar]
  10. Hutton P., Dye J., Prys-Roberts C. An assessment of the Dinamap 845. Anaesthesia. 1984 Mar;39(3):261–267. doi: 10.1111/j.1365-2044.1984.tb07240.x. [DOI] [PubMed] [Google Scholar]
  11. Kiowski W., Erne P., Bertel O., Bolli P., Bühler F. Acute and chronic sympathetic reflex activation and antihypertensive response to nifedipine. J Am Coll Cardiol. 1986 Feb;7(2):344–348. doi: 10.1016/s0735-1097(86)80503-4. [DOI] [PubMed] [Google Scholar]
  12. Kissinger P. T., Bruntlett C. S., Shoup R. E. Neurochemical applications of liquid chromatography with electrochemical detection. Life Sci. 1981 Feb 2;28(5):455–465. doi: 10.1016/0024-3205(81)90138-7. [DOI] [PubMed] [Google Scholar]
  13. Lambert C. R., Hill J. A., Feldman R. L., Pepine C. J. Myocardial ischemia during intravenous nicardipine administration. Am J Cardiol. 1985 Mar 1;55(6):844–845. doi: 10.1016/0002-9149(85)90170-5. [DOI] [PubMed] [Google Scholar]
  14. Lieberman J. Elevation of serum angiotensin-converting-enzyme (ACE) level in sarcoidosis. Am J Med. 1975 Sep;59(3):365–372. doi: 10.1016/0002-9343(75)90395-2. [DOI] [PubMed] [Google Scholar]
  15. Lopez L. M., Mehta J. L., Baz R., Aguila E. Effects of nitrendipine and hydralazine on plasma catecholamines in essential hypertension. Clin Pharmacol Ther. 1984 Oct;36(4):444–450. doi: 10.1038/clpt.1984.202. [DOI] [PubMed] [Google Scholar]
  16. MacGregor G. A., Markandu N. D., Smith S. J., Sagnella G. A. Captopril: contrasting effects of adding hydrochlorothiazide, propranolol, or nifedipine. J Cardiovasc Pharmacol. 1985;7 (Suppl 1):S82–S87. [PubMed] [Google Scholar]
  17. Manhem P., Bramnert M., Hulthén U. L., Hökfelt B. The effect of captopril on catecholamines, renin activity, angiotensin II and aldosterone in plasma during physical exercise in hypertensive patients. Eur J Clin Invest. 1981 Oct;11(5):389–395. doi: 10.1111/j.1365-2362.1981.tb02001.x. [DOI] [PubMed] [Google Scholar]
  18. McGrath B. P., Arnolda L. F. Enalapril reduces the catecholamine response to exercise in patients with heart failure. Eur J Clin Pharmacol. 1986;30(4):485–487. doi: 10.1007/BF00607965. [DOI] [PubMed] [Google Scholar]
  19. Millar J. A., Struthers A. D., Beastall G. H., Reid J. L. Effect of nifedipine on blood pressure and adrenocortical responses to trophic stimuli in humans. J Cardiovasc Pharmacol. 1982;4 (Suppl 3):S330–S334. [PubMed] [Google Scholar]
  20. Ménard J., Guyenne T. T., Corvol P., Pau B., Simon D., Roncucci R. Direct immunometric assay of active renin in human plasma. J Hypertens Suppl. 1985 Dec;3(3):S275–S278. [PubMed] [Google Scholar]
  21. Nakamura N., Soubrier F., Menard J., Panthier J. J., Rougeon F., Corvol P. Nonproportional changes in plasma renin concentration, renal renin content, and rat renin messenger RNA. Hypertension. 1985 Nov-Dec;7(6 Pt 1):855–859. doi: 10.1161/01.hyp.7.6.855. [DOI] [PubMed] [Google Scholar]
  22. Nakaya H., Schwartz A., Millard R. W. Reflex chronotropic and inotropic effects of calcium channel-blocking agents in conscious dogs. Diltiazem, verapamil, and nifedipine compared. Circ Res. 1983 Mar;52(3):302–311. doi: 10.1161/01.res.52.3.302. [DOI] [PubMed] [Google Scholar]
  23. Nievelstein H. M., Van Essen H., Tijssen C. M., Smits J. F., Struyker Boudier H. A. Systemic and regional hemodynamic actions of calcium entry blockers in conscious spontaneously hypertensive rats. Eur J Pharmacol. 1985 Jul 17;113(2):187–198. doi: 10.1016/0014-2999(85)90735-6. [DOI] [PubMed] [Google Scholar]
  24. Pasanisi F., Elliott H. L., Reid J. L. Vascular and aldosterone responses to angiotensin II in normal humans: effects of nicardipine. J Cardiovasc Pharmacol. 1985 Nov-Dec;7(6):1171–1175. doi: 10.1097/00005344-198511000-00025. [DOI] [PubMed] [Google Scholar]
  25. Pham-Huu-Trung M. T., Corvol P. A direct determination of plasma aldosterone. Steroids. 1974 Nov;24(5):587–508. doi: 10.1016/0039-128x(74)90013-0. [DOI] [PubMed] [Google Scholar]
  26. Silke B., Verma S. P., Nelson G. I., Hussain M., Taylor S. H. Haemodynamic dose-response effects of i.v. nicardipine in coronary artery disease. Br J Clin Pharmacol. 1984 Nov;18(5):717–724. doi: 10.1111/j.1365-2125.1984.tb02534.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Simon G., Snyder D. K. Altered pressor responses in long-term nitrendipine treatment. Clin Pharmacol Ther. 1984 Sep;36(3):315–319. doi: 10.1038/clpt.1984.181. [DOI] [PubMed] [Google Scholar]
  28. Zimmerman B. G., Sybertz E. J., Wong P. C. Interaction between sympathetic and renin-angiotensin system. J Hypertens. 1984 Dec;2(6):581–587. doi: 10.1097/00004872-198412000-00002. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES