Effects of inhibition of nitric oxide formation on the regulation of coronary blood flow in anesthetized dogs.
In 11 open-chest dogs with a flowmeter on the left circumflex artery, L-NMMA, a selective inhibitor of nitric oxide-formation, was subselectively infused into the left circumflex artery at a rate of 2.5 mg/ml (ml/min) to avoid systemic hemodynamic effects. The coronary blood flow at normal arterial blood pressure was similar prior to and during L-NMMA infusion. However, when the arterial blood pressure was raised by inflating a balloon in the descending aorta, the nitric oxide suppression induced a dramatic increase in coronary vascular resistance by almost 40% compared to control conditions without L-NMMA infusion at identically elevated arterial blood pressure. L-NMMA induced a significant downward shift and flattening of the pressure-flow relation over a pressure range from 60-150 mmHg. Peak hyperemic coronary flow after 20-s transient coronary occlusion was similar prior to and during L-NMMA infusion, but the duration of the hyperemic flow response was significantly shortened during L-NMMA infusion indicating exaggerated constriction after hyperemic stimulus. The EDRF/nitric oxide-system plays an important role for the regulation of coronary blood flow by counteracting autoregulatory constrictor responses to increased driving pressure and shear stress in the intact canine circulation.
Solzbach
U
U
Department of Internal Medicine III, University of Freiburg, FRG.
Liao
J
J
Eigler
N L
NL
Zeiher
A M
AM
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide