The effects of calcium channel antagonists on coronary nitrite outflow in isolated rat heart.

The aim of the study was to compare the effects of Ca 2+ channel antagonists on coronary endothelial L-arginine/NO system in isolated rat heart. The hearts of male Wistar albino rats (n = 36, age 8 weeks, body mass 180-200 g) were perfused according to Langendorff technique at gradually increased coronary perfusion pressure (CPP) which induced flow-dependent NO release (nitrite outflow). The experiments were performed during control condition or in the presence of different Ca 2+ channel antagonists: nifedipine (CAS 21829-25-4, 30 nmol/l), diltiazem (CAS 42399-41-7, 3 μmol/l), verapamil (CAS 52-53-9, 0.4 μmol/l) or amiodipine (CAS 88150-42-9, 100 nmol/l) were administered separately. Also, nifedipine or amiodipine were administered in combination with an inhibitor of nitric oxide synthase (NOS), L-NAME (N G -nitro-L-arginine-methyl-ester, 30 μmol/l). Coronary flow (CF) varied in autoregulatory range from 3.93 ± 0.25 ml/min/g wt at 50 cmH 2 O to 4.49 ± 0.31 ml/min/g wt at 90 cmH 2 O. In autoregulatory range nitrite outflow varied from 1.80 ± 0.22 nmol/min/g wt at 50 cmH 2 O to 2.21 ± 0.25 nmol/min/g wt at 90 cmH 2 O and was strictly parallel with the CPP-CF (coronary perfusion pressure/coronary flow) curve. The autoregulatory range of CF was significantly extended (40-100 cmH 2 O) under the influence of nifedipine. Hemodynamic effects were accompanied by significant changes in nitrite outflow in all groups except for the verapamil group. Nifedipine and diltiazem induced statistically significant increases of nitrite outflow in coronary venous effluent, strictly parallel with the CPP-CF curve, from 58 % at 120 cmH 2 O to 190 % at 40 cmH 2 O and from 74 % at 120 cmH 2 O to 166 % at 40 cmH 2 O, respectively. On the contrary, amlodipine induced significant reduction of nitrite outflow which was stronger at the lower value of CPP (44-46 % at 40-80 cmH 2 O), compared to the higher value of CPP (32-37 % at 100-120 cmH 2 O). When L-NAME was applied in combination with nifedipine or amlodipine, CF was significantly reduced with parallel changes in nitrite outflow. The results show that Ca 2+ channel antagonists (verapamil, diltiazem, nifedipine and amiodipine) strongly influence the coronary endothelial L-arginine/NO system in isolated rat heart leading to the difference in nitrite outflow.