SYSTEMIC AND CORONARY EFFECTS OF L-NAME, AN INHIBITOR OF ENDOTHELIAL NITRIC-OXIDE SYNTHASE IN CONSCIOUS DOGS

Fourteen mongrel dogs were chronically instrumented on the circumflex coronary artery for measurement of coronary diameter (CD ; Piezoelectric crystals) and coronary blood flow (CBF : Doppler flow probe). Coronary resistance (CR) was calculated as mean arterial blood pressure (MAP)/CBF. Systemic and coronary effects of three intravenous doses of N(G)-nitro-L-arginine (L-NAME : 0,l ; 0,3 ; 1 mg/kg) were recorded (n = 5). Systemic and coronary effects of two vasodilators, acetylchohline (ACH) (endothelium-dependent : 0,3-mu-g/kg) and nitroglycerin (NTG) (endothelium-independent : 1-mu-g/kg) were compared before and after L-NAME (1 mg/kg) (n = 6). Finally, the effects of L-NAME (I mg/kg) were compared one week before and three days after denudation (balloon catheter) of the circumflex coronary artery (2 cm up and downstream from the crystals attachment site). All experiments were performed in conscious dogs. L-NAME induced a dose-dependent constriction of large epicardial coronary arteries [- 1.5 +/- 0.5 % from 3.1 +/- 0.3 mm, p < 0.05 ; - 4.0 +/- 0.7 % from 3.2 mm, p < 0.001 ; - 5.3 +/- 1.2 % from 3,0 mm, p < 0.01 ; respectively]. L-NAME 0.3 and 1 mg/kg induced a significant increase in MAP [+ 12.5 +/- 3.0 % from 90 +/- 4 mmHg, p < 0.01 ; + 11.3 +/- 3.5 % from 96 +/- 7 mmHg, p < 0.05 ; respectively] and CR [+ 18.0 +/- 8.3 % from 9.8 +/- 3.0 mmHg/cm.s, p < 0.01 ; + 18.7 +/- 8,2 % from 10.4 +/- 3.0 mmHg/cm.s, p < 0.01 ; respectively] with a significant bradycardia, but CBF was not modified. Effects of ACH were unchanged after L-NAME. Large coronary artery vasodilation induced by TNG was enhanced after L-NAME [from 7.5 % before L-NAME to 10.8 % after L-NAME ; p < 0.01]. After denudation, L-NAME-induced constriction of large epicardial artery was abolished from - 5.3 +/- 1.2 % before denudation to - 0.7 +/- 0.5 % after denudation, p < 0.01], but other effects were similar. Our results show that nitric oxide synthesis modulates epicardial coronary basal vasomotor tone in conscious dogs. In large epicardial arteries, this basal vasodilator tone is exclusively due to an endothelial nitric oxide synthase. In our experiments, L-NAME has no effect on ACH-induced responses. Finally, we demonstrate the development of a supersensitivity to NTG after inhibition of nitric oxide synthesis in vivo.