Summary
The biological effects of 1-Sarcosine, 8-Threonine angiotensin II ([Sar1, Thr8]ANG II) on blood pressure, plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were investigated in six normal subjects on an unrestricted diet, and compared with those of 1-Sarcosine, 8-Isoleucine ANG II ([Sar1, Ile8]ANG II) and 1-Sarcosine, 8-Alanine ANG II ([Sar1, Ala8]ANG II). All three ANG II analogues (A II A) showed agonistic pressor activity, that of [Sar1, Ile8]ANG II being greater than that of [Sar1, Thr8]ANG II or [Sar1, Ala8]ANG II. The antagonistic effect of [Sar1, Thr8]ANG II on blood pressure was less than [Sar1, Ile8]ANG II or [Sar1, Ala8]ANG II. Both [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II increased PAC and blocked the steroidogenic action of ANG II, while [Sar1, Thr8]ANG II showed little effect on PAC. All three A II A caused similar suppression of PRA and showed no inhibitory effect on the decrease in PRA produced by ANG II. These results indicate that [Sar1, Thr8] ANG II is an A II A with weak agonistic pressor action and that it has vascular selective properties. It is also suggested that ANG II receptors in a variety of target organs are heterogeneous.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Haber E (1976) The role of renin in normal and pathological cardiovascular homeostasis. Circulation 54: 849–861
Davis JO, Freeman RH, Johnson JA, Spielman WS (1974) Agents which block the action of the renin-angiotensin system. Circ Res 34: 279–285
Brunner HB, Gavras H, Laragh JH, Keenan R (1973) Angiotensin II blockade in man by Sar1, Ala8-angiotensin II for understanding and treatment of high blood pressure. Lancet 2: 1045–1048
Streeten DHP, Anderson GH, Freiberg JM, Dalakos TG (1975) Use of an angiotensin II antagonist (Saralasin) in the recognition of “angiotensinogenic” hypertension. N Engl J Med 292: 657–662
Ogihara T, Yamamoto T, Kumahara Y (1974) Clinical application of synthetic angiotensin II analogue. Jpn Circ J 38: 997–1003
Khosla MC, Hall MM, Smeby RR, Bumpus FM (1974) Agonist and antagonist relationship in 1- and 8-substituted analogues of angiotensin II. J Med Chem 17: 1156–1160
Bravo EL, Khosla MC, Bumpus FM (1976) Comparative studies of the humoral and arterial pressure responses to Sar1, Ala8-, Sar1, Ile8- and Sar1, Thr8-angiotensin II in the trained, unanaesthetized dog. In: Stokes GS, Edwards KDG (eds) Progress in biochemical pharmacology. Drugs affecting the renin-angiotensin-aldosterone system. S. Karger, Basel, pp 33–40
Cody RJ, Tarazi RC, Fouad FM, Bravo EL (1980) Hemodynamics of a new angiotensin antagonist, [Sar1, Thr8] AII, in hypertensive man. Circulation 61: 338–344
Case DB, Wallace JM, Keim HJ, Sealey JE, Laragh JH (1976) Usefulness and limitations of saralasin, a partial competitive agonist of angiotensin II, for evaluating the renin and sodium factors in hypertensive patients. Am J Med 60: 825–836
Ogihara T, Hata T, Mikami H, Mandai T, Kumahara Y (1977) Effects of two angiotensin II analogues on blood pressure in normal subjects with various sodium balances. Life Sci 20: 1855–1862
Hata T, Ogihara T, Mikami H, Mandai T, Kumahara Y (1980) Effects of two angiotensin II analogues on blood pressure, plasma aldosterone concentration, plasma renin activity and creatinine clearance in normal subjects on different sodium intakes. Eur J Clin Pharmacol 18: 295–299
Fouad FM, Ceimo JMK, Tarazi RC, Bravo EL (1980) Contrasts and similarities of acute hemodynamic responses to specific antagonism of angiotensin II ([Sar1, Thr8] AII) and to inhibition converting enzyme (Captopril). Circulation 61: 163–169
Beckerhoff R, Uhlschmid G, Vetter WJ, Armbruster H, Nussberger J, Schimid U, Siegenthaler W (1975) The effect of the angiotensin analogue 1-Sar, 8-Ile-angiotensin II on aldosterone and renin secretion in dogs. Acta Endocrinol [Suppl I] 193: 134
Hollenberg NK, Williams GH, Burger B, Ishikawa I, Adams DF (1976) Blockade and stimulation of renal, adrenal and vascular angiotensin II receptors with 1-Sar, 8-Ala angiotensin II in normal man. J Clin Invest 57: 39–46
Bravo EL, Khosla MC, Bumpus FM (1974) Action of [1-Des (Aspartic acid), 8-Isoleucine] angiotensin II upon the pressor and steroidogenic activity of angiotensin II. J Clin Endocrinol Metab 40: 530–533
Sarstedt CA, Vaughan ED Jr, Peach MJ (1975) Selective inhibition by des-Asp1-Ile8-angiotensin II of the steroidogenic response to restricted sodium intake in the rat. Circ Res 37: 350–358
Kono T, Oseko F, Ikeda F, Nanno M, Endo J (1977) Biological activity of high dose of des-asp1-, ileu8-angiotensin II in man. Acta Endocrinol (Copenh) 86: 156–161
Paiva TB, Paiva ACM, Freer RJ, Stewart JM (1972) Alkylating analogs of peptide hormones. 2. Synthesis and properties of p-[N, N-bis (2-chloroethyl) amino] phenylbutryl derivatives of angiotensin II. J Med Chem 15: 6–8
Regoli D, Park WK, Rioux F (1974) Pharmacology of angiotensin. Pharmacol Rev 26: 69–123
Freer RJ, Sutherland JC Jr, Day AR (1980) Synthesis and pharmacology of a noncompetitive antagonist of angiotensin-induced contractions of vascular smooth muscle. [Sarcosyl]1-[Cysteinyl (S-Methyl)]8-angiotensin II. Circ Res 46: 720–725
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hata, T., Ogihara, T., Nakamaru, M. et al. Effect of three angiotensin II antagonists, [Sar1, Thr8]-, [Sar1, Ile8]-and [Sar1, Ala8]angiotensin II on blood pressure and endocrine factors in normal subjects. Eur J Clin Pharmacol 23, 7–10 (1982). https://doi.org/10.1007/BF01061369
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01061369