title: Effects of regional inhibition of nitric oxide synthesis in intact porcine hearts.
abstract: 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.
authors.affiliation: University of Oslo, Institute for Experimental Medical Research, Ullevål Hospital, Norway.
authors.forename: K A
authors.initials: KA
authors.lastname: Kirkebøen
authors.forename: P A
authors.initials: PA
authors.lastname: Naess
authors.forename: J
authors.initials: J
authors.lastname: Offstad
authors.forename: A
authors.initials: A
authors.lastname: Ilebekk
mesh_terms: 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
chemical_list: D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D001120:Arginine; D000241:Adenosine