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 (10-3 × 10 M) and dihydropyridines, amlodipine (10-3 × 10 M), and benidipine (10-10 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% O-5% CO. After a resting period, verapamil, amlodipine, and benidipine were applied cumulatively on serotonin (10 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 pIC value, but not the maximal response, to all blockers were significantly higher than at 37 °C. Hypothermia in the presence of N-nitro-l-arginine methyl ester (L-NAME, 10 M) decreased the pIC and E 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.

Calcium channel blockers are a group of drugs that commonly prescribed to treat cardiovascular disorders such as; hypertension, angina pectoris, peripheral vascular disorders and some arrhythmias. Calcium channel blockers, particularly the newer, longer-acting agents, are clearly effective in reducing elevated blood pressure with minimal to modest adverse effect profiles, therefore they are used extensively. These drugs reduce the amount of calcium entering cells of the heart and blood vessel walls, and they cause vasodilatation especially in arterioles. These drugs commonly block L-type of voltagegated calcium channels. Recent studies have shown that some calcium channel blockers also bind to N-and T-type channels. N-type channels are located in high amounts at the presynaptic terminals of neurons. T-type calcium channels known to be present in cardiac and smooth muscle, and also in many neuronal cells in the central nervous system. Blockage of these two types of channels leads to decreased glomerular capillary pressures, stabilization of the reninangiotensin-aldosterone system, and sympathetic nervous system. As a result, especially new generation of calcium channel blockers have effects that are defined as pleiotropic effects, such as reno-protective, vascular endothelial protective and cardio-protective effects.ÖZET Kalsiyum kanal blokerleri, hipertansiyon, angina, periferik vasküler bozukluklar ve bazı aritmiler gibi kardiyovasküler hastalıkların tedavisinde yaygın olarak kullanılan bir ilaç grubudur. Kalsiyum kanal blokerlerinden özellikle daha yeni, daha uzun etkili olanlar, daha düşük yan etki profilleri ile hipertansiyon tedavisinde oldukça etkilidir. Bu ilaçlar, damar düz kası ve kalp hücrelerinde, sitoplazma membranındaki voltaj-bağımlı kalsiyum kanallarına veya reseptörlere yüksek afinite ile bağlanarak kalsiyum girişini azaltırlar, özellikle arteriyollerde düz kasları gevşeterek güçlü vazodilatasyon yaparlar. Voltaj-bağımlı kalsiyum kanallarının çoğunlukla L-tipine bağlanırlar. Yakın zamanda yapılan çalışmalar, bazı kalsiyum kanal blokerlerinin N-ve T-tipi kanallara da bağlandığını göstermiştir. Bunlardan N-tipi kanallar sempatik sinir uçlarında, T-tipi kanallar ise kardiyak sinus nodu ile afferent ve efferent arteriyollerde bulunur. Bu iki tip kanalın blokajı, glomerüler kapiller basıncın azalmasına, renin-anjiotensin-aldosteron sisteminin ve sempatik sinir sisteminin stabilizasyonuna neden olur. Sonuçta, özellikle yeni jenerasyon kalsiyum kanal blokerleri, renoprotektif, vasküler endotel koruyucu etki ve kardiyoprotektif etkiler gibi pleiotropik etkiler olarak tanımlananan etkilere sahiptirler.