Moderate hypothermia and responses to calcium channel blockers - Role of the nitric oxide

Moderate hypothermia (25-31 degrees C) may have a significant influence on vascular tone. At present, very little is known about the role of endothelial nitric oxide on the hypothermia-induced responses. In this study, we investigated the effect of hypothermia (to 28 degrees C) on the vasodilatation induced by verapamil, a phenylalkylamine calcium channel blocker (10(-9)-3 x 10(-4) M) and dihydropyridines, amlodipine (10(-9)-3 x 10(-4) M), and benidipine (10(-9)-10(-3) M) on 5-hydroxytryptamine (5-HT or serotonin) precontracted calf cardiac veins. Furthermore, the role of nitric oxide in the hypothermia-induced responses was analyzed. Ring preparations of veins obtained from calf hearts were suspended in organ baths containing 15 ml of Krebs-Henseleit solution, maintained at 37 degrees C, and continuously gassed with 95% O-2-5% CO2. After a resting period, verapamil, amlodipine, and benidipine were applied cumulatively on serotonin (10(-6) M) precontracted calf cardiac vein rings and induced concentration-dependent relaxations. In another part of the study, the medium temperature was decreased to 28 degrees C after the preparations were contracted with 5-HT, then cumulative concentrations of verapamil, amlodipine, or benidipine were added. During hypothermia, the pIC(50) value, but not the maximal response, to all blockers were significantly higher than at 37 degrees C. Hypothermia in the presence of N-G-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) decreased the pIC(50) and E-max values to verapamil, amlodipine, and benidipine. Only one blocker was tested in each preparation. These results suggest that nitric oxide may play a role in the hypothermia-induced changes in vasodilation caused by verapamil, amlodipine, and benidipine in calf cardiac vein, but further research is needed to explain the complete mechanism.