Direct in vivo effects of nitric oxide on the coronary circulation.
To determine the direct in vivo effects of nitric oxide (NO) on the coronary circulation, we infused NO-saturated saline (1.0 +/- 0.1 mmol/l) into the coronary arteries of anesthetized dogs and measured changes in coronary blood flow velocity (CBFV) with a Doppler catheter, changes in coronary artery size with quantitative angiography, and transmural myocardial perfusion with radioactive microspheres. Boluses of NO (1-8 micromol) caused a stepwise increase in CBFV (3.1 +/- 0.3 x basal CBFV at 8 micromol) similar to that caused by adenosine (2.6 +/- 0.3 x basal CBFV, maximal dose). Continuous subselective infusions (0.1, 1.0, and 4.0 micromol/min) caused dose-dependent increases in CBFV (2.2 +/- 0.3 x basal CBFV at 4.0 micromol/min) and in epicardial artery diameter (+ 15 +/- 6% diam). Left main infusions (8 micromol/min) caused a stepwise increase in CBFV and in the endocardial-to-epicardial flow ratio without affecting systemic hemodynamics. Brief infusion of NO (2 min) did not significantly reduce acetylcholine-mediated endothelial NO release. Therefore, despite rapid metabolism, direct intra-arterial infusion of NO can be given at a rate sufficient to overwhelm metabolic elimination, providing direct evidence that NO is a potent in vivo coronary vasodilator. Moreover, the enhanced subendocardial vasodilator response to direct NO infusion suggests increased regional sensitivity to NO.
Department of Medicine, University of Minnesota, Minneapolis 55455, USA.
J W
JW
Chambers
G S
GS
Voss
J R
JR
Snider
S M
SM
Meyer
J L
JL
Cartland
R F
RF
Wilson
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D008163:Luminescent Measurements; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology*; D009994:Osmolar Concentration; D010496:Pericardium; D014664:Vasodilation
D009569:Nitric Oxide