Coronary vasodilation to acetylcholine, adenosine and bradykinin in dogs: effects of inhibition of NO-synthesis and captopril.
We investigated the effects of inhibition of both nitric oxide (NO) synthesis and angiotensin converting enzyme (ACE) on agonist-induced relaxations in the coronary system. Chronically instrumented conscious dogs (n = 4) were prepared for the measurement of coronary blood flow (CBF), coronary diameter of the left circumflex artery (LCX), mean arterial blood pressure (MAP) and heart rate (HR). Intracoronary infusions of acetylcholine, adenosine and bradykinin were performed after intracoronary pretreatment of either vehicle, L-NAME (6 mg.kg-1), captopril (1 mg.kg-1) or both L-NAME+captopril. Acetylcholine bradykinin and adenosine caused dose-dependent increases in CBF and LCX. HR increased concomitantly. Captopril potentiated the vasodilating effects of bradykinin and acetylcholine on LCX and CBF significantly (P < or = 0.05) and those of adenosine slightly. L-NAME caused vasoconstriction, hypertension and bradycardia. The effects of acetylcholine on CBF were abolished during L-NAME treatment while bradykinin and adenosine responses were markedly reduced. When captopril and L-NAME were given simultaneously, the vasodilator responses to bradykinin but not to acetylcholine or adenosine were partially restored (P < or = 0.05). We conclude that in vivo, (a) adenosine possibly elicits endothelium-dependent dilation; (b) adenosine and bradykinin act in part independently of the L-arginine/NO pathway; (c) vasodilation to acetylcholine is potentiated by acute ACE inhibition via NO-dependent mechanisms.
Zanzinger
J
J
Department of Applied Physiology, University of Freiburg, Germany.
Bassenge
E
E
D000109:Acetylcholine / Q000502:physiology; D000241:Adenosine / Q000502:physiology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000502:physiology; D002216:Captopril / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004357:Drug Synergism; D005260:Female; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000096:biosynthesis; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide; D001120:Arginine; D002216:Captopril; D000241:Adenosine; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester