ANGIOTENSIN(1-7) IS AN ANTAGONIST AT THE TYPE-1 ANGIOTENSIN-II RECEPTOR

Objective: The present study investigated the antagonism of the amino- terminal heptapeptide fragment of angiotensin II {[des-Phe(8)]-angiote nsin II; Ang(1-7)} to angiotensin II (Ang II) both in vitro in rabbit aortae and in vivo in rats. Methods and results: In rabbit isolated en dothelium intact aortic rings Ang(1-7) caused a concentration-related rightward displacement of the Ang II curve and depressed the maximum r esponse to Ang II. By applying the data to a Schild plot an apparent p A(2) of 5.5 was calculated. This depression of maximum response could be reversed by co-incubation of Ang(1-7) with the competitive angioten sin antagonist losartan. Ang(1-7) had no effect on the contractile res ponses of several other agonists. Intravenous infusion of 10 or 100 mu g/kg per min Ang(1-7) had no effect on the resting blood pressure in the anaesthetized rat but inhibited Ang II-induced presser responses. Conclusion: The present results show that Ang(1-7) is a specific non-c ompetitive antagonist of Ang II at type 1 angiotensin II receptors.