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 microM), 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 approximately 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.
Okada
T
T
Department of Physiology, Juntendo University School of Medicine, Tokyo, Japan.
Izawa
N
N
Nakamura
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects*; D019332:Endothelin-1 / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D015737:Nisoldipine / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D019332:Endothelin-1; D014665:Vasodilator Agents; D019335:Nitroarginine; D015737:Nisoldipine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D009543:Nifedipine