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Comparative effects of angiotensin II and its degradation products angiotensin III and angiotensin IV in rat aorta
Author(s) -
Li Q.,
Zhang J.,
Pfaffendorf M.,
Zwieten P.A.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb15951.x
Subject(s) - tachyphylaxis , losartan , angiotensin ii , medicine , angiotensin ii receptor type 1 , endocrinology , angiotensin iii , chemistry , renin–angiotensin system , schild regression , antagonist , receptor , angiotensin receptor , biology , blood pressure
1 In the present study, the contractile effects of angiotensin III (AIII) and angiotensin IV (AIV) compared with those of angiotensin II (All) were determined in rat aortic ring preparations. 2 All three peptides caused concentration‐dependent contractions with similar maximal responses. AIII proved approximately 4 times less potent than All, whereas AIV was about 1000 times less active than AII 3 The selective AT 1 ‐receptor antagonist, losartan (10–300 nM) caused parallel rightward shifts of the concentration‐response curves (CRC) for all three peptides. The Schild plot slopes for the effect of losartan on AIII curves were significantly lower than unity ( P <0.05). The selective AT 2 ‐receptor antagonist, PD123177 did not influence the CRCs for All and AIV. However, the AIII curves were moderately shifted leftward in the presence of PD123177 (0.1 and 1 μ m ). 4 Destruction of the endothelium or incubation with the NO‐synthesis inhibitor N G ‐monomethyl‐ l ‐arginine acetate ( l ‐NMMA) (0.1 m m ) significantly enhanced the contractile responses to all three peptides. 5 Tachyphylaxis was investigated by constructing a second CRC for all three peptides, after an interval of 1 h. The presence of endothelium significantly enhanced the development of tachyphylaxis to all three peptides. However, in endothelium‐denuded preparations, the E max value of the second curve elicted by All was about 50%, compared with the first one, whereas for AIII and AIV E max values were as high as 90% and 100%, respectively. 6 Our results indicate that both AIII and AIV are less potent but similarly efficacious vasoconstrictor agents compared with AII Their contractile effects are also mediated by AT 1 receptors and probably modulated by endothelium. Tachyphylaxis induced by AIII and AIV proved weaker than that for AII Tachyphylaxis appears to be enhanced by the presence of an intact endothelium.