Endothelium-mediated regulation of coronary tone

Publisher Website
Google Scholar
Abstract
To what extent endothelial autacoids like endothelium-derived relaxant factor/nitric oxide (EDRF/NO), in addition to neural-humoral factors, are involved in the regulation of myocardial perfusion, is presently not known. Therefore, we investigated in conscious, chronically instrumented dogs the effect of stereospecific inhibitors (NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine (L-NNA), NG-monomethylester-L-arginine (L-NAME)) of nitric oxide-synthesis and -release on epicardial coronary tone (and coronary diameter) and myocardial perfusion. A hydraulic coronary cuff was used, to produce reactive hyperemia and to keep the myocardial perfusion constant over short periods. 40 mg/kg L-NNA i. v. caused a long-lasting increase in mean arterial blood pressure from 94±8 to 129±11 mmHg and a simultaneous decrease in coronary diameter by 2.8±0.3%. Heart rate dropped from 87 to 58 min−1, but the double product of heart rate and blood pressure dropped by only 8±2% (p = 0.05). The maximal coronary conductance during peak reactive hyperemia (after 20 s ischemia) indicating complete coronary dilation was diminished by 48% after L-NNA. The severe drop in resting myocardial perfusion and O2-supply, and nearly unchanged rate pressure product and thus myocardial metabolic rate following the inhibition of nitric oxide formation demonstrate a substantial contribution of EDRF/NO to the regulation of myocardial perfusion.