Abstract
1. The function of angiotensin converting enzyme was investigated in twenty-four healthy men. Forearm blood flow was measured under basal conditions and during administration of enalaprilat (a converting enzyme inhibitor) and/or peptide substrates of converting enzyme into the left brachial artery. Blood flow was compared in the two arms. 2. Enalaprilat had no effect on basal blood flow. The concentration of enalaprilat in venous blood from the control arm was low, and plasma renin activity was not increased, indicating that systemic inhibition of converting enzyme did not occur. 3. Effects of angiotensin and of bradykinin, administered intra-arterially, were limited to the infused arm. Enalaprilat (13 nmol min-1) inhibited converting enzyme in the infused arm, in which it caused approximately a 100-fold reduction in sensitivity to angiotensin I, while having no effect on the vasoconstriction caused by angiotensin II. Enalaprilat increased vasodilatation caused by bradykinin. 4. Aspirin, an inhibitor of cyclo-oxygenase, did not inhibit vasodilatation caused by bradykinin whether infused alone or with enalaprilat, indicating that these responses are not mediated by prostaglandins. 5. We conclude that under basal conditions neither conversion of angiotensin I to angiotensin II nor degradation of bradykinin determines resistance vessel tone in the human forearm. Converting enzyme may affect vascular tone in situations in which intravascular concentrations of peptides are increased over those present under basal conditions.
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- Barrow S. E., Cockcroft J., Dollery C. T., Hickling N. E., Ritter J. M. Identification of 13,14-dihydro-15-oxo-prostaglandin F2 alpha in the circulation during infusions of bradykinin and prostaglandin E2 in man. Br J Pharmacol. 1987 May;91(1):245–250. doi: 10.1111/j.1476-5381.1987.tb09005.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barrow S. E., Dollery C. T., Heavey D. J., Hickling N. E., Ritter J. M., Vial J. Effect of vasoactive peptides on prostacyclin synthesis in man. Br J Pharmacol. 1986 Jan;87(1):243–247. doi: 10.1111/j.1476-5381.1986.tb10177.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biollaz J., Schelling J. L., Jacot Des Combes B., Brunner D. B., Desponds G., Brunner H. R., Ulm E. H., Hichens M., Gomez H. J. Enalapril maleate and a lysine analogue (MK-521) in normal volunteers; relationship between plasma drug levels and the renin angiotensin system. Br J Clin Pharmacol. 1982 Sep;14(3):363–368. doi: 10.1111/j.1365-2125.1982.tb01992.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackwell G. J., Flower R. J. Glucocorticoids, lungs and prostaglandins. Bull Eur Physiopathol Respir. 1981;17(4):595–607. [PubMed] [Google Scholar]
- Brock T. A., Rittenhouse S. E., Powers C. W., Ekstein L. S., Gimbrone M. A., Jr, Alexander R. W. Phorbol ester and 1-oleoyl-2-acetylglycerol inhibit angiotensin activation of phospholipase C in cultured vascular smooth muscle cells. J Biol Chem. 1985 Nov 15;260(26):14158–14162. [PubMed] [Google Scholar]
- Burch R. M., Knapp D. R., Halushka P. V. Vasopressin stimulates thromboxane synthesis in the toad urinary bladder: effects of imidazole. J Pharmacol Exp Ther. 1979 Sep;210(3):344–348. [PubMed] [Google Scholar]
- Caldwell P. R., Seegal B. C., Hsu K. C., Das M., Soffer R. L. Angiotensin-converting enzyme: vascular endothelial localization. Science. 1976 Mar 12;191(4231):1050–1051. doi: 10.1126/science.175444. [DOI] [PubMed] [Google Scholar]
- Campbell D. J. Circulating and tissue angiotensin systems. J Clin Invest. 1987 Jan;79(1):1–6. doi: 10.1172/JCI112768. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cherry P. D., Furchgott R. F., Zawadzki J. V., Jothianandan D. Role of endothelial cells in relaxation of isolated arteries by bradykinin. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2106–2110. doi: 10.1073/pnas.79.6.2106. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Damas J., Deby C. Sur la libération des prostaglandines et de leurs précurseurs, par la bradykinine. Arch Int Physiol Biochim. 1976 Apr;84(2):293–304. doi: 10.3109/13813457609073980. [DOI] [PubMed] [Google Scholar]
- Dixon C. M., Fuller R. W., Barnes P. J. The effect of an angiotensin converting enzyme inhibitor, ramipril, on bronchial responses to inhaled histamine and bradykinin in asthmatic subjects. Br J Clin Pharmacol. 1987 Jan;23(1):91–93. doi: 10.1111/j.1365-2125.1987.tb03015.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dorer F. E., Kahn J. R., Lentz K. E., Levine M., Skeggs L. T. Hydrolysis of bradykinin by angiotensin-converting enzyme. Circ Res. 1974 Jun;34(6):824–827. doi: 10.1161/01.res.34.6.824. [DOI] [PubMed] [Google Scholar]
- Erdös E. G. The angiotensin I converting enzyme. Fed Proc. 1977 Apr;36(5):1760–1765. [PubMed] [Google Scholar]
- FOX R. H., GOLDSMITH R., KIDD D. J., LEWIS G. P. Bradykinin as a vasodilator in man. J Physiol. 1961 Aug;157:589–602. doi: 10.1113/jphysiol.1961.sp006745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferreira S. H., Vane J. R. The disappearance of bradykinin and eledoisin in the circulation and vascular beds of the cat. Br J Pharmacol Chemother. 1967 Jun;30(2):417–424. doi: 10.1111/j.1476-5381.1967.tb02148.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Förstermann U., Hertting G., Neufang B. The role of endothelial and non-endothelial prostaglandins in the relaxation of isolated blood vessels of the rabbit induced by acetylcholine and bradykinin. Br J Pharmacol. 1986 Mar;87(3):521–532. doi: 10.1111/j.1476-5381.1986.tb10194.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GREENFIELD A. D., PATTERSON G. C. Reactions of the blood vessels of the human forearm to increases in transmural pressure. J Physiol. 1954 Sep 28;125(3):508–524. doi: 10.1113/jphysiol.1954.sp005177. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hong S. L. Effect of bradykinin and thrombin on prostacyclin synthesis in endothelial cells from calf and pig aorta and human umbilical cord vein. Thromb Res. 1980 Jun 15;18(6):787–795. doi: 10.1016/0049-3848(80)90201-7. [DOI] [PubMed] [Google Scholar]
- Kelly J. G., Doyle G., Donohue J., Laher M., Vandenburg M. J., Currie W. J., Cooper W. D. Pharmacokinetics of enalapril in normal subjects and patients with renal impairment. Br J Clin Pharmacol. 1986 Jan;21(1):63–69. doi: 10.1111/j.1365-2125.1986.tb02823.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- LECOMTE J., TROQUET J. [Antagonism between bradykinin and phenylbutazone in the rabbit]. C R Seances Soc Biol Fil. 1960;154:1115–1117. [PubMed] [Google Scholar]
- LENTZ K. E., SKEGGS L. T., Jr, WOODS K. R., KAHN J. R., SHUMWAY N. P. The amino acid composition of hypertensin II and its biochemical relationship to hypertensin I. J Exp Med. 1956 Aug 1;104(2):183–191. doi: 10.1084/jem.104.2.183. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mendelsohn F. A. Localization and properties of angiotensin receptors. J Hypertens. 1985 Aug;3(4):307–316. doi: 10.1097/00004872-198508000-00002. [DOI] [PubMed] [Google Scholar]
- Millar J. A., Leckie B. J., Morton J. J., Jordan J., Tree M. A microassay for active and total renin concentration in human plasma based on antibody trapping. Clin Chim Acta. 1980 Feb 14;101(1):5–15. doi: 10.1016/0009-8981(80)90050-9. [DOI] [PubMed] [Google Scholar]
- Needleman P., Marshall G. R., Sobel B. E. Hormone interactions in the isolated rabbit heart. Synthesis and coronary vasomotor effects of prostaglandins, angiotensin, and bradykinin. Circ Res. 1975 Dec;37(6):802–808. doi: 10.1161/01.res.37.6.802. [DOI] [PubMed] [Google Scholar]
- Ng K. K., Vane J. R. Conversion of angiotensin I to angiotensin II. Nature. 1967 Nov 25;216(5117):762–766. doi: 10.1038/216762a0. [DOI] [PubMed] [Google Scholar]
- Ng K. K., Vane J. R. Fate of angiotensin I in the circulation. Nature. 1968 Apr 13;218(5137):144–150. doi: 10.1038/218144a0. [DOI] [PubMed] [Google Scholar]
- Palmer R. M., Ferrige A. G., Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature. 1987 Jun 11;327(6122):524–526. doi: 10.1038/327524a0. [DOI] [PubMed] [Google Scholar]
- Patrono C., Ciabattoni G., Pinca E., Pugliese F., Castrucci G., De Salvo A., Satta M. A., Peskar B. A. Low dose aspirin and inhibition of thromboxane B2 production in healthy subjects. Thromb Res. 1980 Feb 1;17(3-4):317–327. doi: 10.1016/0049-3848(80)90066-3. [DOI] [PubMed] [Google Scholar]
- Regoli D., Barabé J. Pharmacology of bradykinin and related kinins. Pharmacol Rev. 1980 Mar;32(1):1–46. [PubMed] [Google Scholar]
- Ryan J. W., Ryan U. S., Schultz D. R., Whitaker C., Chung A. Subcellular localization of pulmonary antiotensin-converting enzyme (kininase II). Biochem J. 1975 Feb;146(2):497–499. doi: 10.1042/bj1460497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SKEGGS L. T., Jr, LENTZ K. E., KAHN J. R., SHUMWAY N. P., WOODS K. R. The amino acid sequence of hypertensin. II. J Exp Med. 1956 Aug 1;104(2):193–197. doi: 10.1084/jem.104.2.193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ulm E. H. Enalapril maleate (MK-421), a potent, nonsulfhydryl angiotensin-converting enzyme inhibitor: absorption, disposition, and metabolism in man. Drug Metab Rev. 1983;14(1):99–110. doi: 10.3109/03602538308991383. [DOI] [PubMed] [Google Scholar]
- Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
- Vargaftig B. Effet des analgésiques non narcotiques sur l'hypotension due à la bradykinine. Experientia. 1966 Mar 15;22(3):182–183. doi: 10.1007/BF01897724. [DOI] [PubMed] [Google Scholar]
- WHITNEY R. J. The measurement of volume changes in human limbs. J Physiol. 1953 Jul;121(1):1–27. doi: 10.1113/jphysiol.1953.sp004926. [DOI] [PMC free article] [PubMed] [Google Scholar]