Angiotensin-(1-7) antagonist A-779 attenuates the potentiation of bradykinin by captopril in rats.
We evaluated the possibility that endogenous angiotensin-(1-7) [Ang-(1-7)] could participate in the potentiation of bradykinin (BK) by the angiotensin-converting enzyme inhibitor (ACEI) captopril in conscious Wistar rats. Catheters were introduced into descending aorta (through the left carotid artery) for BK injection, femoral artery for arterial pressure measurement, and both femoral veins for BK injection and vehicle or Ang-(1-7) antagonist, A-779 infusion. Infusion of vehicle or A-779 started 40 to 45 minutes after captopril administration. Sequential BK dose-response curves were made before, 10 minutes after captopril, and within 10 minutes of infusion of vehicle or A-779. To evaluate angiotensin I conversion, dose-response curves for angiotensin I and angiotensin II were made following the same protocol used for BK. Captopril treatment markedly increased the BK hypotensive effect and significantly decreased angiotensin I conversion. Infusion of A-779 did not modify the angiotensin II pressor effect or the effect of captopril on angiotensin I conversion. However, A-779 significantly reduced the potentiating effect of captopril on the hypotensive effect of BK administered intravenously or intra-arterially. These results suggest that endogenous Ang-(1-7) and/ or an Ang-(1-7)-related peptide plays an important role in the BK potentiation by ACEI through a mechanism not dependent upon inhibition of ACE hydrolytic activity.
Maia
Luciana Gonçalves
LG
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Ramos
Marcela Caldeira
MC
Fernandes
Liliam
L
de Carvalho
Maria Helena Catelli
MH
Campagnole-Santos
Maria José
MJ
Souza dos Santos
Robson Augusto
RA
D000803:Angiotensin I / Q000037:antagonists & inhibitors*; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001920:Bradykinin / Q000378:metabolism*; D002216:Captopril / Q000494:pharmacology*; D004357:Drug Synergism; D006973:Hypertension / Q000188:drug therapy; D007261:Infusions, Intra-Arterial; D007262:Infusions, Intravenous; D008297:Male; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C092006:7-Ala-angiotensin (1-7); D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000804:Angiotensin II; D000803:Angiotensin I; D002216:Captopril; C118790:angiotensin I (1-7); D001920:Bradykinin