title: Potentiation of the hypotensive effect of bradykinin by short-term infusion of angiotensin-(1-7) in normotensive and hypertensive rats.
abstract: In this study we evaluated the effect of angiotensin-(1-7) on the hypotensive action of bradykinin (BK) in normotensive rats, renal hypertensive rats (RHR), and spontaneously hypertensive rats (SHR). In addition, we evaluated the effect of angiotensin-converting enzyme (ACE) inhibition with enalaprilat treatment (10 mg/kg I.V.) on the BK-potentiating activity of Ang-(1-7). Renal hypertension was produced by aorta coarctation between the origin of renal arteries. Ang-(1-7) (0.3 pmol/min) or saline (0.9% NaCl, 5 microL/min) was infused intravenously in conscious male Wistar rats, adult SHR, or RHR. Intravenous bolus injections of BK (0.1 to 1.6 nmol in RHR and SHR; 0.625 to 5 nmol in Wistar rats) were made before and within 30 and 60 minutes of Ang-(1-7) infusion. Ang-(1-7) infusion did not change mean arterial pressure (MAP) of Wistar rats (MAP=97+/-3 mm Hg), RHR (MAP=173+/-3 mm Hg), or SHR (MAP=177+/-5 mm Hg). In Wistar rats, Ang-(1-7) increased the BK hypotensive effect by 24+/-6% within 60 minutes of infusion. No significant changes were observed at 30 minutes of infusion. In additional groups of rats, Ang-(1-7) (5 pmol/min, n=5) was infused alone or combined with its selective antagonist D-Ala7-Ang-(1-7) (A-779) (5 pmol/min, n=6). The bradykinin-potentiating activity of Ang-(1-7) was completely abolished by A-779. In SHR and RHR, Ang-(1-7) significantly increased the hypotensive effect of BK by 59+/-8% and 57+/-9.8%, respectively, within 60 minutes of infusion. No significant changes were observed with saline infusion. In Wistar rats, enalaprilat treatment increased the BK-potentiating activity of Ang-(1-7) transforming the effect of 0.3 pmol/min into that observed with a rate 16-fold higher (5 pmol/min). On the other hand, in SHR enalaprilat did not change the Ang-(1-7) effect, while it abolished the BK potentiation in RHR. Our data show that the BK-potentiating activity of Ang-(1-7) is preserved and even augmented in hypertensive rats. The finding that the BK-potentiating activity of Ang-(1-7) could be demonstrated at a very low infusion rate suggests that this angiotensin can act as an endogenous modulator of the vascular actions of kinins. ACE inhibition can influence differently the BK-potentiating activity of Ang-(1-7) in normotensive and hypertensive rats.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federale de Minas Gerais, Belo Horizonte, Brazil.
authors.forename: C V
authors.initials: CV
authors.lastname: Lima
authors.forename: R D
authors.initials: RD
authors.lastname: Paula
authors.forename: F L
authors.initials: FL
authors.lastname: Resende
authors.forename: M C
authors.initials: MC
authors.lastname: Khosla
authors.forename: R A
authors.initials: RA
authors.lastname: Santos
mesh_terms: D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001920:Bradykinin / Q000494:pharmacology*; D004357:Drug Synergism; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar
chemical_list: D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin