Martínez Ana Cristina, Hernández Medardo, Prieto Dolores, Raposo Rafaela, Pagán Rosa María, García-Sacristán Albino, Benedito Sara
Sección Departamental de Fisiología Animal, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Vascul Pharmacol. 2006 Jan;44(1):34-41. doi: 10.1016/j.vph.2005.09.004. Epub 2005 Nov 11.
The present study was designed to establish whether penile dorsal arteries isolated from rabbits fed a high cholesterol diet show an enhanced contractile and/or impaired vasodilator response to histamine, and to characterize the histamine receptor subtype involved through in vitro isometric techniques. New Zealand White rabbits were fed a normal diet or a 1% cholesterol diet for 16 weeks. Arteries from cholesterol-fed rabbits retained the ability to relax in response to acetylcholine, whereas histamine and noradrenaline induced a greater contraction response compared to that observed in controls. In both groups, histamine-induced contraction was unaffected by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), its precursor L-arginine or the cyclooxygenase inhibitor indomethacin. Treatment of arterial rings in the control and hypercholesterolemia groups with the H1 receptor antagonist, mepyramine, unmasked a vasodilation response to histamine. This was followed by contraction at higher concentrations showing a leftward displacement of the histamine curve compared to controls. The histamine receptor that induced contraction in preparations from the hypercholesterolemic animals was of the H1 subtype, whereas the receptor involved in histamine-induced relaxation was H2. The affinity of histamine receptor agonists was comparable to their effects in control animals, and receptor antagonists showed the same potency in both groups. Our findings indicate a preserved endothelial function and enhanced contraction in response to histamine in penile dorsal arteries, probably due to a change in the sensitivity of the contractile machinery of smooth muscle but not a mechanism mediated by a receptor.
本研究旨在确定从喂食高胆固醇饮食的兔子分离出的阴茎背动脉是否对组胺表现出增强的收缩反应和/或受损的血管舒张反应，并通过体外等长技术表征所涉及的组胺受体亚型。新西兰白兔分别喂食正常饮食或1%胆固醇饮食16周。喂食胆固醇的兔子的动脉保留了对乙酰胆碱作出舒张反应的能力，而与对照组相比，组胺和去甲肾上腺素诱导出更大的收缩反应。在两组中，组胺诱导的收缩不受一氧化氮合酶抑制剂NG-硝基-L-精氨酸甲酯（L-NAME）、其前体L-精氨酸或环氧化酶抑制剂吲哚美辛的影响。用H1受体拮抗剂美吡拉敏处理对照组和高胆固醇血症组的动脉环，揭示了对组胺的血管舒张反应。随后在较高浓度下出现收缩，与对照组相比，组胺曲线向左移位。在高胆固醇血症动物的制剂中诱导收缩的组胺受体是H1亚型，而参与组胺诱导舒张的受体是H2。组胺受体激动剂的亲和力与其在对照动物中的作用相当，受体拮抗剂在两组中显示出相同的效力。我们的研究结果表明，阴茎背动脉的内皮功能得以保留，对组胺的收缩反应增强，这可能是由于平滑肌收缩机制的敏感性发生了变化，而不是由受体介导的机制。
