Interaction of bradykinin and angiotensin-(1-7) in the central modulation of the baroreflex control of the heart rate.
OBJECTIVE
Previous studies have shown that angiotensin-(1-7) potentiates the vascular actions of bradykinin. In the present study, we evaluated the interaction of bradykinin and angiotensin-(1-7) in the central modulation of baroreflex control of the heart rate.


METHODS
Blood pressure and reflex bradycardia, elicited by intravenous injection of phenylephrine, were evaluated in conscious male Wistar rats before and at the end of 1 h of an intracerebroventricular infusion of angiotensin-(1-7) at 0.5 or 1.0 microg/h combined with bradykinin at 2.5 microg/h; or angiotensin-(1-7) at 2.0 microg/h combined with bradykinin at 4.0 microg/h; or angiotensin-(1-7) alone at 2.0 or 4.0 microg/h; or bradykinin alone at 4.0 or 8.0 microg/h; or saline at 8 microl/h. In addition, baroreflex bradycardia was evaluated before and at the end of 1 and 2 h of intracerebroventricular infusion of angiotensin-(1-7) at 4 microg/h for 2 h; or saline at 8 microl/h in the first hour followed by HOE 140 at 90 ng/h in the second hour; or angiotensin-(1-7) at 4 microg/h in the first hour followed by angiotensin-(1-7) at 4 microg combined with HOE 140 at 90 ng/h in the second hour; or HOE 140 at 90 ng/h in the first hour followed by HOE 140 at 90th ng/h combined with angiotensin-(1-7) at 4 microg/h in the second hour; or saline at 8 microl/h for 2 h.


RESULTS
The intracerebroventricular infusion of angiotensin-(1-7) or bradykinin alone required a dose of 4.0 and 8.0 microg/h, respectively, to facilitate baroreflex control of the heart. However, a simultaneous infusion of these peptides at subeffective rates was able to produce a significant increase in baroreflex sensitivity. In addition, the facilitation of the baroreflex control of the heart rate induced by angiotensin-(1-7) at 4.0 microg/h was inhibited by HOE 140.


CONCLUSIONS
These results suggest that centrally, bradykinin and angiotensin-(1-7) can interact in order to modulate baroreflex control of the heart rate. In addition, our data indicate that the central modulatory effect of angiotensin-(1-7) on the baroreflex is mediated, at least in part, by the release of kinins.
Bomtempo
C A
CA
Departamento de Fisiologia e Biofisica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil.
Santos
G F
GF
Santos
R A
RA
Campagnole-Santos
M J
MJ
D000319:Adrenergic beta-Antagonists; D000803:Angiotensin I; D000804:Angiotensin II / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D065168:Bradykinin Receptor Antagonists; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D065168:Bradykinin Receptor Antagonists; D010446:Peptide Fragments; D000804:Angiotensin II; C065679:icatibant; D000803:Angiotensin I; C118790:angiotensin I (1-7); D001920:Bradykinin