Comparison of the effects of nifedipine and nisoldipine on coronary vasoconstriction in the Langendorff-perfused rat heart

By using Langendorff-perfused rat hearts, we compared the relaxant effects of two dihydropyridine calcium antagonists (nifedipine and nisoldipine) on the coronary vasculature, Hearts were perfused at a constant flow rate (13 ml/min), and the coronary perfusion pressure was monitored to assess vasoconstriction and relaxation. Administration of 5 nM endothelin significantly increased the perfusion pressure within 5 min, and it did not decrease during the subsequent 10-min washout period. Washout with 1 nM nisoldipine or 10 nM nifedipine almost completely normalized the perfusion pressure. Administration of a nitric oxide synthase inhibitor, N-G- nitro-L-arginine (100 mu M), elevated the perfusion pressure at 5 min. When 1 nM nifedipine was added to the perfusate, it failed to decrease the pressure, but 10 and 100 nM nifedipine partly decreased it (96.4 +/- 8.2 and 87.0 +/- 8.8 mm Hg for 10 and 100 nM, respectively). Nisoldipine alleviated the pressure elevation almost completely at 10 nM (60.0 +/- 5.2 mm Hg). The vasodilatory effect of nisoldipine was also similar to 10 times more potent than that of nifedipine when coronary vasoconstriction was induced by hypoxia-reoxygenation. These results suggest that nisoldipine has a stronger effect than nifedipine at the organ level, which does not depend on the cause of coronary vasoconstriction.