Effects of regional inhibition of nitric oxide synthesis in intact porcine hearts.
The importance of nitric oxide (NO) in coronary blood flow (CBF) regulation was examined in anesthetized pigs. NO synthesis was inhibited by intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine (L-NNA). L-NMMA (30 mumol/min) reduced CBF (Doppler flowmetry) by 16.3% (13.1-20.2%; P < 0.001) and L-NNA (30 mumol/min) by 16.1% (13.9-18.9%; P < 0.001). During NO blockade, myocardial oxygen consumption was unaltered as an increase in oxygen extraction occurred due to a reduced partial pressure of oxygen and oxygen saturation in blood from the anterior interventricular vein. L-Arginine completely reestablished CBF after giving L-NMMA, but not after giving L-NNA. L-NNA reduced the coronary flow response to ADP by 66-83%, whereas the selected dose of L-NMMA did not affect it. The flow response to adenosine was not affected by either L-NMMA or L-NNA. L-NNA reduced reactive hyperemia after occluding the left anterior descending coronary artery for 10 and 30 s but not for 120 s. Our data show that NO produced in the coronary endothelium plays an important role in CBF regulation in vivo, accounting for approximately 16% of CBF and a major part of the flow response to ADP. NO also contributes to reactive hyperemia after brief, but not longer, ischemic periods.
Kirkebøen
K A
KA
University of Oslo, Institute for Experimental Medical Research, Ullevål Hospital, Norway.
Naess
P A
PA
Offstad
J
J
Ilebekk
A
A
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006439:Hemodynamics; D006940:Hyperemia / Q000209:etiology / Q000503:physiopathology; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D010101:Oxygen Consumption / Q000187:drug effects; D013552:Swine; D013997:Time Factors; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D001120:Arginine; D000241:Adenosine