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 nitric oxide (NO) formation by an arginine analogue on basal and stimulated NO release in conductance and resistance coronary vessels.

METHODS

In 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 omega-nitro-L-arginine methyl ester (L-NAME, 50.0 micrograms.kg-1 min-1 for 12 min) to block NO synthesis.

RESULTS

Before L-NAME, ACH increased 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, ACH-induced increases in CD (0.184 +/- 0.053 mm) were not altered. L-NAME did not change CBF responses to NTG but increased CD responses (0.345 +/- 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/min, P < 0.01). Increases in CD created by ADENO, a flow-dependent phenomenon, 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 effects of L-NAME on CBF and CD responses to ACH and ADENO continuously delivered into the coronary artery were similar to those of boluses.

CONCLUSIONS

L-NAME selectively reduced ACH-induced dilation in resistance coronary vessels but failed to prevent responses of conductance coronary vessels in spite of reducing baseline CD and blocking flow-dependent effects of ADENO. Therefore, blockade of NO formation resulted in disparate effects on receptor-operated dilation of resistance and conductance coronary vessels.