EFFECTS OF ANGIOTENSIN-II ANTAGONISTS ON THE CONTRACTILE AND HYDROSMOTIC EFFECT OF AT-II AND AT-III IN THE TOAD (BUFO-ARENARUM)

The effects of peptide and non-peptide angiotensin II receptor antagon ists on the responses to angiotensin II were examined using aortic rin gs and skin isolated from the toad. The contractile responses of aorti c rings to (Ala-Pro-Gly) angiotensin II were inhibited by the angioten sin II analogue Leu(8) angiotensin II, with a pA(2) value of 7.6. Simi larly, the concentration response curve for (Ala-Pro-Gly) angiotensin II was displaced to the right by the specific angiotensin receptor sub type antagonist DuP 753, with a pA(2) value of 6.0. In contrast, the a ngiotensin receptor subtype 2 antagonists PD 123177 and CGP 42112A did not modify the contractile response to (Ala-Pro-Gly) angiotensin II. None of the antagonists was able to alter the contractile response to norepinephrine. Both Leu(8) angiotensin II (10(-8) mol . l(-1))and DuP 753 (10(-6) mol . l(-1)) partially inhibited angiotensin III-induced contractions in toad aorta. Angiotensin III, in turn, exhibited lower activity than [Asn(1)-Val(5)] angiotensin II in this preparation, its molar potency ratio being 0.293. Previous work from this laboratory re ported that osmotic water permeability in the skin of the toad Bufo ar enarum was increased by angiotensin II, the effect being blocked by th e peptide antagonist Leu(8) angiotensin II. The hydrosmotic response t o [Asn(1)-Val(5)] angiotensin II (10(-7) mol . l(-1)) was significantl y inhibited by DuP 753 (10(-6) and 5 x 10(-6) mol . l(-1)), whereas th e response was not inhibited by a tenfold higher concentration of eith er PD 123177 or CGP 42112A. DuP 753 (10(-6) mol . l(-1))also inhibited the hydrosmotic response to angiotensin III (10(-7) mol . l(-1)). The se results suggest that receptors for angiotensin II present in isolat ed toad aorta and skin exhibit pharmacological features similar to tho se characterized as angiotensin subtype 1 in mammalian tissues.