The effects of moderate hypothermia (28 °C) on the response of human varicose spermatic vein to α1-adrenoceptor agonist phenylephrine and the role of endothelial nitric oxide (NO) in these effects were studied. Concentration–response curves for phenylephrine (10−9 to 3 × 10−4 M) were recorded in rings with and without endothelium at 37 and 28 °C. To further analyze the role of NO, in the response to phenylephrine during hypothermia, the effects of this agonist in the presence of NG-nitro-L-arginine methyl ester (10−4 M) were also determined. Under every condition tested, phenylephrine produced a marked, concentration-dependent contraction. Sensitivity of intact veins to the agonist was consistently lower at 28 °C than at 37 °C. There was no significant difference in phenylephrine response at 28 and 37 °C in vessels without endothelium but at 28 °C veins without endothelium showed a higher sensitivity than intact veins to phenylephrine. The sensitivity of veins with and without endothelium to nitroprusside (10−9 to 3 × 10−3 M) was significantly decreased during hypothermia, and endothelium removal did not affect the relaxation to this nitrovasodilator. These results suggest that moderate hypothermia decreases the sensitivity of human varicose spermatic vein to phenylephrine probably by increasing the availability of endothelial NO.
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 NG-nitro-l-arginine methyl ester (L-NAME, 10−4 M) decreased the pIC50 and Emax 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.
Authors:KE Nurullahoğlu-Atalık, S Kutlu, H Solak and R Özen Koca
Statins have cholesterol-independent effects including an increased vascular nitric oxide activity and are commonly used by patients with cardiovascular disease. Such patients frequently have cardiovascular diseases, which may be treated with cilostazol, a platelet aggregation inhibitor. This study was designed to investigate whether combined use of cilostazol would increase the inhibitory effect of statin on vascular smooth muscle and how maturation would affect these responses. Female Wistar rats, aged 3–4 months (young) and 14–15 months (adult), were sacrificed by cervical dislocation and the thoracic aorta was dissected and cut into 3- to 4-mm-long rings. The rings were mounted under a resting tension of 1 g in a 20-ml organ bath filled with Krebs–Henseleit solution. Rings were precontracted with phenylephrine (10−6 M), and the presence of endothelium was confirmed with acetylcholine (10−6 M). Then, the concentration–response curves were obtained for atorvastatin alone (10−10 to 3 × 10−4 M; control) and in the presence of cilostazol (10−6 M) in young and adult rat aortas. This experimental protocol was also carried out in aorta rings, which had been pretreated with NG-nitro-l-arginine methyl ester (l-NAME, 10−4 M). Atorvastatin induced concentration-dependent relaxations in young and adult rat thoracic aorta rings precontracted with phenylephrine. The pIC50 value of atorvastatin was significantly decreased in adult rat aortas. In addition, pretreatment of aortas with cilostazol enhanced the potency of atorvastatin in both young and adult aortas. Incubation with l-NAME did not completely eliminate the relaxations to atorvastatin in the presence of cilostazol. These results suggest that combined application of cilostazol with atorvastatin was significantly more potent than atorvastatin alone. Combined drug therapy may be efficacious in delaying the occurrence of cardiovascular events.