Summary
In low- and normal- renin hypertensive patients, but not in high-renin patients, the acute antihypertensive response to the angiotensin-converting enzyme (ACE) inhibitor captopril was completely blocked by aprotinin-induced kallikrein inhibition. Blood pressure reduction with long-term ACE inhibition could be overcome only in part by aprotinin. It is proposed that in low- and normal-renin hypertension the vasodepressor effect of acute ACE inhibition is mainly due to kinin accumulation. Conversely, in high-renin patients a fall in angiotensin II concentration accounts for the hypotensive response to captopril. From the pressor effect of aprotinin in chronically captopril treated patients it appears that kinins are also involved in the blood pressure reduction with long-term ACE inhibition. The finding that ACE inhibition and kallikrein blockade produced predictable and opposite effects on blood pressure suggests broad participation of changes in depressor kinin production in the control of vascular tone in essential hypertension.
Zusammenfassung
Bei essentiellen Hypertonikern mit niedriger und normaler Plasmareninaktivität, nicht dagegen bei Patienten mit hohen Reninwerten, konnte der akute antihypertensive Effekt einer Angiotensin-Converting-Enzym-(ACE) Blockade mit Captopril durch eine Aprotinin-induzierte Kallikreinblockade vollständig verhindert werden. Nach chronischer ACE-Hemmung ließ sich die Blutdrucksenkung nur zum Teil durch Aprotinin aufheben. Die Ergebnisse weisen darauf hin, daß bei essentieller Hypertension mit normaler und niedriger Reninaktivität der blutdrucksenkende Effekt einer akuten ACE-Hemmung im wesentlichen Folge einer Kinin-Akkumulation ist. Dagegen scheint bei Patienten mit hoher Reninaktivität eine Abnahme der Angiotensin II-Konzentration für die antihypertensive Wirkung von Captopril verantwortlich zu sein. Der pressorische Effekt von Aprotinin bei Patienten unter Langzeittherapie mit Captopril weist darauf hin, daß Kinine auch für die unter chronischer ACE-Hemmung auftretende Blutdrucksenkung mitverantwortlich sind. Die Beobachtung, daß ACE-Inhibition und Kallikrein-Blockade voraussagbare und gegensinnige Effekte auf den Blutdruck hervorrufen, läßt eine Beteiligung des Kallikrein-Kinin-Systems an der Kontrolle des Gefäßtonus bei essentieller Hypertension vermuten.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Case DB, Atlas SA, Laragh JH, Sealey JE, Sullivan PA, McKinstry DN (1978) Clinical experience with blockade of the renin-angiotensin-aldosterone system by an oral convertingenzyme inhibitor (SQ 14,225, captopril) in hypertensive patients. Prog Cardiovasc Dis 21:195–206
Cody RJ Jr, Tarazi RC, Bravo EL, Fouad FM (1978) Hemodynamics of orally-active converting enzyme inhibitor (SQ 14,225) in hypertensive patients. Clin Sci Mol Med 55:453–459
Gavras H, Brunner HR, Turini GA, Kershaw GR, Tifft CP, Cuttelod S, Gavras I, Vukovich RA, McKinstry DN (1978) Antihypertensive effect of the oral angiotensin converting-enzyme inhibitor SQ 14,225 in man. N Engl J Med 298:991–995
Johnston CI, McGrath BP, Millar JA, Matthews PG (1979) Long-term effects of captopril (SQ 14,225) on blood pressure and hormone levels in essential hypertension. Lancet 2:493–496
Overlack A, Stumpe KO, Heck I, Krück F (1980) Neues Prinzip in der Langzeitbehandlung der essentiellen Hypertension. Dtsch Med Wochenschr 15:505–509
Swartz SL, Williams GH, Hollenberg NK, Moore TJ, Dluhy RG (1979) Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation. Hypertension 1:106–111
Swartz SL, Williams GH, Hollenberg NK, Levine L, Dluhy RG, Moore TJ (1980) Captopril-induced changes in prostaglandin production. J Clin Invest 65:1257–1264
Erdös EG (1977) The angiotensin I converting enzyme. Fed Proc 36:1760–1765
McCaa RE, Hall JE, McCaa CS (1978) The effects of angiotensin I-converting enzyme inhibitors on arterial blood pressure and urinary sodium excretion. Role of the renal renin-angiotensin and kallikrein-kinin systems. Circ Res 43 [Suppl I]:132–139
Williams GH, Hollenberg NK (1977) Accentuated vascular and endocrine response to SQ 20881 in hypertension. N Engl J Med 297:184–188
Matthews G, McGrath B, Johnston C (1979) Hormonal changes with long-term converting enzyme inhibition by captopril in essential hypertension. Proceedings of the 6th Scientific Meeting of the International Society on Hypertension, Göteborg, June 11–13, p 156
McCarthy DA, Potter DE, Nicolaides ED (1965) An in vivo estimation of the potencies and half-lives of synthetic bradykinin and kallidin. J Pharmacol Exp Ther 148:117–122
Cushman DW, Cheung HS, Sabo EF, Ondetti MA (1977) Design of potent competitive inhibitors of angiotensin-converting enzyme. Biochemistry 16:5484–5491
Fritz H, Fink E, Truscheit E (1979) Kallikrein inhibitors. Fed Proc 38:2753–2759
Haber E, Koerner T, Page LB, Kliman B, Purnode A (1969) Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects. J Clin Endocrinol 29:1349–1355
Vetter W, Vetter H, Siegenthaler W (1973) Radioimmunoassay for aldosterone without chromatography. 2. Determination of plasma aldosterone. Acta Endocrinol (Kbh) 74:558–567
Cushman DW, Cheung HS (1971) Spectrophotometric assay and properties of the angiotensin-converting enzyme of rabbit lung. Biochem Pharmacol 20:1637–1648
Spech HJ, Wernze H, Weiss H (1976) Radioimmunoassay of angiotensin II and its metabolites. Comparison of two different extraction procedures. Acta Endocrinol (Kbh) 202:67–72
Morton JJ, Casals-Stenzel J, Lever AF, Miller JA, Riegger AJG, Tree M (1979) Inhibitors of the reninangiotensin system in experimental hypertension: with a note on the measurement of angiotensin I, II and III during infusion of converting enzyme inhibitor. Br J Clin Pharmacol 7:[Suppl. 2] 233
Rubin B, Antonaccio MJ (1980) Captopril. Pharmacology of antihypertensive drugs. Raven Press, New York
Blumberg AL, Denny SE, Marshall GR, Needleman P (1977) Blood vessel-hormone interactions: angiotensin, bradykinin, and prostaglandins. Am J Physiol 232:H305-H310
Tuvemo T, Wide L (1973) Prostaglandin release from the human umbilical artery in vitro. Prostaglandins 4:689–694
Carretero OA, Miyazaki S, Scicli AG (1979) Role of kinins in the antihypertensive effects of converting enzyme inhibitor. 6th Scientific Meeting of the International Society of Hypertension, Göteborg, p 18 (Abstracts)
Lee TC, Kushiro T, Gassia J-P, Girolami J, Lupu AN, Maxwell MH (1979) The kallikrein-kinin-system in blood pressure homeostasis. Clin Sci 57:255s-258s
Sealey JE, Atlas SA, Laragh JH, Oza NB, Ryan JW (1979) Activation of a prorenin-like substance in human plasma by trypsin and by urinary kallikrein. Hypertension 1:179–189
Derkx FHM, Tan-Tjiong HL, Man Int'T Veld AJ, Schalekamp MPA, Schalekamp MADH (1979) Activation of inactive plasma renin by plasma and tissue kallikreins. Clin Sci 57:351–357
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Overlack, A., Stumpe, K.O., Kühnert, M. et al. Evidence for participation of kinins in the antihypertensive effect of converting enzyme inhibition. Klin Wochenschr 59, 69–74 (1981). https://doi.org/10.1007/BF01477285
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01477285