CONTRASTING EFFECTS OF BLOCKADE OF NITRIC-OXIDE FORMATION ON RESISTANCE AND CONDUCTANCE CORONARY VESSELS IN CONSCIOUS DOGS

Objectives: To determine the differential effects of blockade of nitri c oxide (NO) formation by an arginine analogue on basal and stimulated NO release in conductance and resistance coronary vessels. Methods: I n conscious dogs, instrumented for measuring coronary blood flow (CBF) and external epicardial coronary artery diameter (CD), intracoronary (ic) acetylcholine (ACH, 3.0 ng/kg), adenosine (ADENO 100.0 ng/kg) and nitroglycerin (NTG, 10.0 ng/kg) were injected before and after ic N-o mega-nitro-L-arginine methyl ester (L-NAME, 50.0 mu g . kg(-1) min(-1) for 12 min) to block NO synthesis. Results: Before L-NAME, ACH increa sed CBF by 65.3 +/- 9.0 from 42.4 +/- 2.9 ml/min and CD by 0.199 +/- 0 .035 from 3.374 +/- 0.193 mm. L-NAME failed to alter baseline CBF but reduced (P < 0.01) CD to 3.220 +/- 0.199 mm. CBF responses to ACH were smaller (P < 0.01) (32.8 +/- 5.3 ml/min) after L-NAME. In contrast, A CH-induced increases in CD (0.184 +/- 0.053 mm) were not altered. L-NA ME did not change CBF responses to NTG but increased CD responses (0.3 45 +/- 0.062 vs 0.217 +/- 0.043 mm, P < 0.01). ADENO-induced increases in CBF were smaller after L-NAME (46.5 +/- 5.6 vs 79.8 +/- 10.9 ml/mi n, P < 0.01). Increases in CD created by ADENO, a flow-dependent pheno menon, were nearly abolished after L-NAME (0.043 +/- 0.018 vs 0.195 +/ - 0.026 mm, P < 0.01) and partially restored by ic L-arginine. The eff ects of L-NAME on CBF and CD responses to ACH and ADENO continuously d elivered into the coronary artery were similar to those of boluses. Co nclusions: L-NAME selectively reduced ACH-induced dilation in resistan ce coronary vessels but failed to prevent responses of conductance cor onary vessels in spite of reducing baseline CD and blocking flow-depen dent effects of ADENO. Therefore, blockade of NO formation resulted in disparate effects on receptor-operated dilation of resistance and con ductance coronary vessels.