Pressor responses to alligator Angiotensin I and some analogs in the spectacled caiman (Caiman crocodilus).
Discovery of the chemical structure of alligator (Alligator mississipiensis) [Asp(1), Val(5), Ala(9)]-Angiotensin I (ANG I) has permitted the investigation of cardiovascular responses to this peptide and its analogs in spectacled caimans (Caiman crocodilus), close relatives of alligators. ANG I and [Asp(1), Val(5)]- Angiotensin II (ANG II) i.v. gave dose-dependent increases in mean arterial pressure but there was no pressor response to [Val(4)]-ANG III (ANG III). Pressor responses to a series of doses of ANG II were compared with a range of doses of norepinephrine (NE) and epinephrine (E) which were found to be only about 1/100 as potent as ANG II on a molar basis. The replacement of d-leu(10)in the alligator ANG I molecule with l-leu(10) almost stopped its conversion to ANG II and attenuated the pressor response. [Asp(1), Val(5), Ala(9)]-ANG I (1-9), and ANG (1-7) both failed to increase arterial blood pressure, even at the relatively high non-physiological test dose of 194pmolkgbw(-1) i.v. Captopril blocked angiotensin converting enzyme (ACE) and prevented the pressor response to ANG I whereas the mammalian AT(1) inhibitor Losartan attenuated, but did not completely block the pressor response to ANG II. These are the first experiments which test the cardiovascular responses to alligator ANG I and its analogues in any crocodilian species.
Department of Zoology, Ramsay Wright Laboratories, Medical Sciences Building, University of Toronto, Toronto, Ont., Canada M5S 3G5. dbutler@zoo.utoronto.ca
David G
DG
Butler
D000489:Alligators and Crocodiles / Q000378:metabolism / Q000502:physiology*; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000805:Angiotensin III / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology
D000959:Antihypertensive Agents; D000804:Angiotensin II; D000805:Angiotensin III; D000803:Angiotensin I; D002216:Captopril; D019808:Losartan; D009638:Norepinephrine; D004837:Epinephrine