Effects of captopril on responses to bradykinin in the hindquarters vascular bed of the rat.
The effects of captopril, and angiotensin converting enzyme (ACE) inhibitor, on responses to bradykinin (BK), to angiotensin (Ang) I and II, and to other agonists were investigated in the hindquarters vascular bed of the rat. Under conditions of controlled flow, intra-arterial (i.a.) injections of BK in doses of 0.1-1.0 microgram, produced dose related decreases in hindquarters perfusion pressure and evoked decreases in systemic arterial pressure. Intra-arterial injections of Ang I and II produced dose-related increases in hindquarters perfusion pressure. Following administration of captopril in a dose of 2 mg/kg i.v., vasodilator responses to i.a. injections of BK were only slightly enhanced in the hindquarters vascular bed, whereas the evoked systemic vasodepressor responses to i.a. injections of BK were markedly enhanced by the ACE inhibitor. Captopril significantly reduced vasoconstrictor responses to i.a. injections of Ang I, whereas vasoconstrictor responses to i.a. injections of Ang II were significantly enhanced. The ACE inhibitor did not significantly alter vasodilator responses to i.a. injections of acetylcholine, nitroglycerin, nitric oxide, albuterol, or pinacidil. The present data show that BK has potent vasodilator activity in the hindquarters vascular bed of the rat and suggest that the site of action is most likely upstream from the site of inactivation, whereas the site of action of Ang I is at or near the site of conversion to Ang II in the hindquarters vascular bed. The observation that the evoked systemic vasodepressor responses to i.a. injections of BK were greatly enhanced, suggest that the lung is the major site of inactivation of BK.
Nossaman
B D
BD
Department of Anesthesiology, Tulane University Medical Center, New Orleans, LA 70112-2699, USA. nossaman@tmc.tulane.edu
Kaye
A D
AD
Kang
B
B
Feng
C J
CJ
Kadowitz
P J
PJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects*; D006614:Hindlimb / Q000098:blood supply*; D007269:Injections, Intra-Arterial; D008168:Lung / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D014665:Vasodilator Agents; D002216:Captopril; D001920:Bradykinin