A New, Long-Lasting Competitive Inhibitor of Angiotensin

Abstract

An analog of angiotensin II, [Sar(1), Ile(8)]-angiotensin II, has a potent and long-lasting competitive antagonistic effect against angiotensin II when tested for its myotropic action on the isolated rabbit aorta and for its effect on blood pressure in anesthetized cats and dogs. Compared to [Ile(8)]-angiotensin II, the new analog has equal antagonistic potency on the isolated system but a much greater potency in vivo. It is assumed that sarcosine in position 1 protects the peptide against enzymatic degradation and enhances its half-life. This study demonstrates that the modification in both positions 1 and 8 are important for the in vivo antagonistic potencies of angiotensin analogs.

Angiotensin II-induced depolarizations in hamster submandibular ganglion neurons.

“…14) , losartan, a selective non-peptide AT 1 receptor antagonist 13) , and PD-123,319 ditrifluoroacetate, a potent selective non-peptide AT 2 receptor antagonist 13) , were respectively applied to cells at concentrations of 10M through perfusate. Losartan was a gift from Merk & Co., Inc.…”

Dynamic Ca2+ signalling in rat arterial smooth muscle cells under the control of local renin‐angiotensin system

“…Thus, endothelium-derived factors are not responsible for the generation of Ca¥ ripples. We then investigated the effect of 10 nÒ [Sar 1 ,IleÌ]-Ang II, an Ang II antagonist (Turker et al 1972). Indeed, Ca¥ ripples were reversibly abolished by the antagonist (Fig.…”

Evidence that the apparent complexity of receptor antagonism by angiotensin II analogues is due to a reversible and syntopic action

“…For example, it has been reported that some peptide analogues did not behave in a simple competitive manner with All, but produced 'non-competitive' or 'insurmountable' antagonism (Regoli et al, 1974;Freer et al, 1980a,b;Koziarz & Moore, 1989; Bovy & Blaine, 1989). The antagonism of [Sar',Ile8]AII, however, has been described as both 'essentially competitive' (Turker et al, 1972) and 'pseudo-irreversible' (Scanlon & Moore, 1988). Most peptide analogues have been found to produce partial agonist effects in vivo (Streeten & Anderson, 1984;Holck et al, 1989; and some in vitro (Regoli et al, 1974;Scanlon et al, 1984;Criscione et al, 1990).…”