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

Canbolat, S and Nurullahoglu Atalik, KE (2018) Moderate hypothermia and responses to calcium channel blockers – Role of the nitric oxide. Physiology International, 105 (1). pp. 53-60. ISSN 2498-602X

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Abstract

Moderate hypothermia (25–31 °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 °C) on the vasodilatation induced by verapamil, a phenylalkylamine calcium channel blocker (10⁻⁹–3 × 10⁻⁴ M) and dihydropyridines, amlodipine (10⁻⁹–3 × 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 °C, and continuously gassed with 95% O₂–5% 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 °C after the preparations were contracted with 5-HT, then cumulative concentrations of verapamil, amlodipine, or benidipine were added. During hypothermia, the pIC₅₀ value, but not the maximal response, to all blockers were significantly higher than at 37 °C. Hypothermia in the presence of N^G-nitro-<sc>l</sc>-arginine methyl ester (L-NAME, 10⁻⁴ M) decreased the pIC₅₀ 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.

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