Summary
The density of angiotensin II (Ang II) receptors on the platelet and the vascular responsiveness to infused angiotensin II before and after two weeks of captopril therapy were examined in ten healthy male volunteers. There was a significant increase in blood flow to the forearm, but no significant changes in either the density of angiotensin II receptors or the pressor response to infused angiotensin II following captopril therapy. The study demonstrates that long term reduction of angiotensin II formation by captopril in man does not increase the responsiveness of the receptors to infused angiotensin, nor results in an „up regulation“ of the angiotensin receptors. It also provides further evidence that some of the long term vasodilator effects of captopril may be mediated by mechanisms other than inhibition of angiotensin I (Ang I) converting enzyme.
Similar content being viewed by others
References
Atkinson BG, Robertson JIS (1979) Captopril in the treatment of clinical hypertension and cardiac failure. Lancet 2: 836–839
Aiken JW (1974) Effects of prostaglandin synthesis inhibitors on angiotensin tachyphylaxis in the isolated cardiac and mesenteric arteries of rabbit. Pol J Pi Pharmacol 26: 217–227
Clough DP, Hatton R, Keddie JR, Collis MG (1982) Hypotensive action of captopril in spontaneously hypertensive and normotensive rats — Interference with neurogenic vasoconstriction. Hypertension 4: 764–772
Davies RO, Gomez HJ, Irvin JD, Walker JF (1984) An overview of the clinical pharmacology of enalapril. Br J Clin Pharmacol 18: 215S-229S
Douglas J, Catt K (1976) Regulation of angiotensin II receptors in the rat adrenal cortex by dietary electrolytes. J Clin Invest 58: 834–843
Douglas J, Saltman S, Fredlund P, Kondo T, Catt KJ (1976) Receptor binding of angiotensin II and antagonists: Correlation with aldosterone production by isolated canine adrenal glomerulose cells. Circ Res 38 [Supp 2]: 108–112
Erdös EG (1975) Angiotensin I converting enzyme. Circ Res 36: 247–255
Finnerty FA (1962) Haemodynamics of angiotensin in man. Circulation XXV: 255–259
Fraser JP, Wood AJJ (1979) Alteration in beta-receptor density following prolonged propranolol treatment. Circulation 60: 274
Fruncilo RJ, Rotmensch HH, Vlasses PH, Koplin JR, Monsell K, Clementi RA, Ferguson RK (1983) Effects of captopril and hydrochlorothiazide on the pressor responses to norepinephrine and angiotensin II in hypertensives. Clin Pharm Ther 33: 2: 226
Galant SP, Duriset L, Underwood S, Insel PA (1978) Beta-adrenergic receptors on polymorphonuclear leukocytes: Adrenergic therapy decreases receptor number. N Engl J Med 299: 933–936
Gunther S, Gimbrone MA, Alexander RW (1980) Regulation by angiotensin II of its receptors in resistance blood vessels. Nature 287: 230–232
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
Johnston CI, Clappison GH, Anderson WP, Yasujina M (1982) Effect of angiotensin-converting enzyme inhibition on circulating and local renin levels. Am J Med 49: 1401–1404
Koletsky RJ, Murray BG, Leboff MS, Moore TJ, Dluhy RG, Hollenberg NK, Williams GH (1984) Captopril enhances vascular and adrenal responsiveness to angiotensin II in essential hypertension. Clin Sci 66: 299–305
Lin SY, Goodfriend TL (1970) Angiotensin receptors. Am J Physiol 218 [5]: 1319–1328
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193: 265–275
Moore AF, Bumpus FM, Khairallah PA (1977) New approaches to the study of angiotensin tachyphylaxis. Mayo Clinic Proc 52: 446–448
Moore TJ, Williams GH (1981) Angiotensin II receptors on human platelets. Circ Res 51 [3]: 314–320
Nies AS, Aarons RD, Gal J, Bramwell HL, Molinoff PB (1979) Increased density of beta adrenergic receptors on lymphocyte following propranolol treatment. Clin Res 19: 445A
Paiva TB, Miyamoto ME, Juliano L, Paiva ACM (1977) Requirements of angiotensin tachyphylaxis in smooth muscle. J Pharmacol Exp Ther 202: 294–300
Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51: 660–672
Swartz SL, Williams GH (1982) Angiotensin-converting enzyme inhibition and prostaglandins. Am J Cardiol 49: 1405–1409
Swartz SL, Williams GH, Hollenberg NK, Crantz FR, Moore TJ, Levine L, Sasahara AA, Dluhy RG (1980) Endocrine profile in the long-term phase of converting-enzyme inhibition. Clin Pharmacol Ther 28: 499–508
Thurston H, Laragh JH (1975) Prior receptor occupancy as determinant of the pressor activity of infused angiotensin II in the rat. Circ Res 36: 113
Whitney RJ (1953) The measurement of volume changes in human limbs. J Physiol (Lond) 121: 1–27
Wright BM, Dore CF (1970) A random-zero sphygmomanometer. The Lancet 1: 337–338
Yutaka I, Keishi A, Masahide S, Toshiaki H, Jire T, Makito S, Toshikazu G, Masoa H, Yutaka K, Kaoru Y, Hiroshi S (1982) Attenuation of pressor responses to norepinephrine and pitressin and potentiation of pressor response to angiotensin II by captopril in human subjects. Hypertension 4: 444–451
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kondowe, G.B., Kelly, J.G., Copeland, S. et al. The effect of chronic captopril therapy on platelet angiotensin II receptor density and vascular responsiveness to angiotensin II infusion. Eur J Clin Pharmacol 31, 525–530 (1987). https://doi.org/10.1007/BF00606624
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00606624