Identification of angiotensinogenic hypertension in man using 1-sar-8-ala-angiotensin II (Saralasin, P-113).

Abstract

Peripheral plasma renin activity (PRA) is not invariably elevated in patients whose ischemic renal lesion is causing hypertension. Infusions of an angiotensin II antagonist, 1-sar-8-ala-angiotensin II (P-113), have been used to determine whether the blood pressure responses might indicate angiotensin dependence in 221 consecutive hypertensive patients. In 32 patients P-113 infusion reversibly reduced blood pressure, and almost all of these "P-113 responders" had elevated renal vein and/or peripheral PRA levels, together with evidence of renal ischemia. Among the 189 "P-113 nonresponders," peripheral PRA was elevated in seven (3.8%), and renal vein PRA ratio was abnormal in two patients, who might represent exceptions to the otherwise successful record of the P-113 response in identifying "angiotensinoginic" hypertensives.

Angiotensin II and Sodium as Determinants of the Agonistic-Antagonistic Balance of Saralasin's Actions

“…ANG II analogues with antagonistic actions, such as [Sar',Ala 8 ] -ANG II (Pals et al, 1971), have provided useful tools to elucidate angiotensin's role 1974;Streeten et al, 1975;Brown et al, 1976;Case et al, 1976;McGregor & Dawes, 1976;Fagard et al, 1977a, b;Noth et al, 1977;Posternak et al, 1977;Fagard et al, 1978c;Van Hoogdalem et al, 1978). However, saralasin possesses intrinsic agonistic angiotensin-like activities on the vascular smooth muscle, on the adrenal gland and possibly on the renal receptors involved in the direct suppression of renin by ANG II (Case et al, 1976;Hollenberg et al, 1976;McGregor & Dawes, 1976;Anderson et al, 1977;Bumpus & Khosla, 1977;Noth et al, 1977;Brown et al, 1978;Fagard et al, 1978a;Williams et al, 1978;Agabiti-Rosei et aI., 1979;Donker et al, 1979;Williams et al, 1979).…”

“…The antagonistic properties of angiotensin II (ANG II) analogues, such as [Sar 1,Ala8)ANG II (saralasin) (Pals, Masucci, Sipos & Denning, 1971) have been used to study the physiological (McGregor & Dawes, 1976;Fagard, Amery, Reybrouck, Lijnen, Moerman, Bogaert & De Schaepdryver, 1977b;Noth, Tan & Murrow, 1977' Posternak, Brunner, Gavras & Brunner, 1977Fagard, Amery, Reybrouck, Lijnen, Billiet, Bogaert, Moerman & De Schaepdryver, 1978c) and pathophysiological (Brunner, Gavras, Laragh & Keenan, 1974;Streeten, Freiberg, Anderson & Dalakos, 1975;Brown, Brown, Fraser, Lever, Morton, Robertson, Rosei & Trust, 1976;Case, Wallace, Keirn, Sealy & Laragh, 1976;Fagard, Amery, Lijnen & Reybrouck, 1977a;Van Hoogdalem, Donker & Leenen, 1978) role of ANG II in normo-and hyper-tension. However, saralasin and other analogues are not devoid of intrinsic agonistic angiotensin-like activity (Bumpus & Khosla, 1977) so that caution is required in the interpretation of the results.…”

“…In the present paper we study three possible angiotensin-like activities of saralasin: its effects on the vascular, on the adrenal and on the renal receptors for ANG II. It has become clear that saralasin, particularly in sodium-replete conditions, may raise arterial pressure (Streeten et al, 1975;Case et al, 1976;Hollenberg, Williams, Burger, Ishikawa & Adams, 1976;McGregor & Dawes, 1976;Anderson, Streeten & Dalakos, 1977;Fagard et al, 1977a;Noth et al, 1977) and renal vascular resistance (Hollenberg et al, 1976), increase plasma aldosterone levels (Noth et al, 1977;Brown, Tucker, Tue, Wisgerhof & Salassa, 1978;Fagard, Lijnen, Amery & Reybrouck, 1978a;Williams, Hollenberg, Brown & Mershey, 1978;Agabiti-Rosei, Brown, Brown, Fraser, Trust, Lever, Morton & Robertson, 1979;Donker, Van Hoogdalem, Pratt & Leenen, 1979) and possibly suppress renin activity (Hollenberg et al, 1976;McGregor & Dawes, 1976;Noth et al, 1977;Williams et al, 1978). When plasma renin and angiotensin levels rise in response to sodium restriction blood pressure usually falls during saralasin (Brunner et aI., 1974;Streeten et al, 1975;Brown et al, 1976;Case et al, 1976;McGregor & Dawes, 1976;Fagard et al, 1977a;Noth et al, 1977;Posternak et al, 1977;Fagard et al, 1978c;Van Hoogdalem et al, 1978), plasma aldosterone decreases or remains unchanged (Brown et al, 1976;Noth et al, 1977;Brown et al, 1978;Fagard et al, 1978a;Williams et al, 1978;Agabiti-Rosei et al, 1979;Donker et aI., ...…”

Effects of 1‐sar‐8‐ala‐angiotensin Ii on Systemic and Pulmonary Haemodynamics in Hypertensive Patients

“…In the sodium-depleted patients, saralasin induced a decrease in arterial pressure associated with a drop in total peripheral resistance (Fig. l), suggesting that arterial pressure is at least partly angiotensin 11-dependent in these conditions (Streeten et al, 1975;Brown e f al., 1976;Case et al, 1976;Briinner et al, 1976). In these patients the initial transient increase in pressure was also observed, though it was less pronounced than in the sodium-replete patients (Fig.…”

“…role of angiotensin I1 in the maintenance of arterial pressure in the hypertensive patient, both in sodium-replete and sodium-depleted conditions (Streeten et al, 1975;Brown et al, 1976;Briinner et al, 1976;Case et al, 1976;Gavras et al, 1976;Fagard et al, 1977). In general, saralasin has no hypotensive effect in sodium-replete conditions, except in severe high renin hypertension, while it decreases pressure in sodium-restricted conditions, even in low renin patients after sufficient sodium depletion.…”