Blockade of the pressor response to angiotensins I and II in the bullfrog, Rana catesbeiana.
We examined the effects of three angiotensin II (AII) analogs, [Sar1,Ala8] AII, [Sar1,Ile8] AII, and [Sar1,Thr8] AII, phenoxybenzamine and captopril on the pressor response to angiotensins I (AI) and II (AII) and norepinephrine (NE) in the bullfrog, Rana catesbeiana. Injection of AI and AII at 0.25, 0.5, and 1.0 micrograms/kg, or NE at 3 micrograms/kg elicited dose-dependent rises in blood pressure. [Sar1,Ile8] AII (10 micrograms/kg/min) significantly blocked the pressor effects of all AI and AII doses. [Sar1,Ala8] AII blocked only the highest dose, and [Sar1,Thr8] AII produced no blockade. Captopril (0.1 mg/kg bolus + 0.5 mg/kg/hr) significantly reduced the response to AI, but not AII or NE. Phenoxybenzamine (5-10 mg bolus + 1 mg/kg/hr) blocked NE, and partially inhibited (36-49%) the pressor effects of AI and AII. These results demonstrate that (1) [Sar1,Ile8] AII is a potent angiotensin antagonist in the bullfrog, while [Sar1,Ala8] AII is partially effective and [Sar1,Thr8] AII is largely ineffectual; (2) captopril is an effective converting enzyme inhibitor; and (3) a portion of the angiotensin response can be inhibited by alpha-receptor blockade and is apparently due to catecholamine release.
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D009638:Norepinephrine / Q000494:pharmacology*; D010643:Phenoxybenzamine / Q000494:pharmacology; D011674:Pulse / Q000187:drug effects*; D011892:Rana catesbeiana; D013329:Structure-Activity Relationship
D000809:Angiotensins; D010643:Phenoxybenzamine; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; D009638:Norepinephrine