Kinin contribution to renal vasodilator effect of captopril in rabbit.
This study was conducted to examine the role of bradykinin in the persistence of the renal vasodilator effect of captopril during angiotensin II receptor blockade. Blood pressure and renal blood flow were monitored in eight groups of pentobarbital-anesthetized rabbits. In group 4, captopril alone was administered, and it decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 21 +/- 4 ml/min. After a bolus injection and a constant intravenous infusion of the imidazole derivative angiotensin II receptor antagonist DuP 753 (group 5), captopril decreased blood pressure by 9 +/- 2 mm Hg and increased renal blood flow by 8 +/- 1 ml/min (12 +/- 1% change in renal blood flow, p less than 0.05 versus group 4). In the presence of a constant intravenous infusion of saralasin (group 6), captopril decreased blood pressure by 13 +/- 5 mm Hg and increased renal blood flow by 7 +/- 2 ml/min (17 +/- 5% change in renal blood flow, p less than 0.05 versus group 4). These results did not differ from those in group 5. During a constant intrarenal arterial infusion of a B2 bradykinin receptor antagonist, DArg0, [Hyp3-Thi5,8-DPhe7]-bradykinin (BkA) (group 7), captopril decreased blood pressure by 14 +/- 4 mm Hg and increased renal blood flow by 10 +/- 4 ml/min. Combined administration of DuP 753 intravenously and BkA intra-arterially (group 8) eliminated the effect of captopril. In group 8, captopril caused insignificant changes in blood pressure and renal blood flow. The results indicate that DuP 753 and saralasin antagonize the renin-angiotensin system to a comparable extent in vivo. Although blockade of the latter system accounted for a significant part of the increase in renal blood flow caused by captopril, the remaining component was contributed by endogenous bradykinin.
Hajj-ali
A F
AF
Department of Pharmacology, University of Minnesota, Minneapolis 55455.
Zimmerman
B G
BG
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D019808:Losartan; D011817:Rabbits; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors; D012079:Renal Circulation / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D018002:Receptors, Bradykinin; D017981:Receptors, Neurotransmitter; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D012504:Saralasin; D019808:Losartan; D001920:Bradykinin