Pressor responses to alligator Angiotensin I and some analogs in the spectacled caiman ( Caiman crocodilus)

Abstract

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 10in 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 194 pmol kg bw −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.