Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension：effect of sildenafil

作     者：Serap Gur Suresh C. Sikka Gillian E. Knight Geoffrey Bumstock Wayne J.G. Hellstrom 

作者机构：Department of Urology Tulane University Health Sciences Center New Orleans LA 70112 USA Autonomic Neuroscience Centre Royal Free and University College Medical School Rowland Hill Street London NW32PF UK 

出 版 物：《Asian Journal of Andrology》 (亚洲男性学杂志（英文版）)

年 卷 期：2010年第12卷第3期

页      面：415-421,I0012页

核心收录：

学科分类：10[医学] 

主　　题：hypertensive rat NG-nitro-L-arginine methyl ester purinergic receptors P2X sildenafil vas deferens 

摘      要：Hypertension （HTN） is a risk factor for erectile dysfunction, but its effect on vas deferens （VD） contractility and the ejaculatory response has not been delineated. NG-nitro-L-arginine methyl ester （L-NAME）, a nitric oxide synthase inhibitor, was used for induction of nitric oxide （NO）-deficient HTN. Our aim was to evaluate the effects of L-NAME-induced HTN on rat VD contractility and to determine whether sildenafil affects VD contractility. A total of 36 male rats were divided into （1） control, （2）L-NAME-HTN, （3） sildenafil treated L-NAME-HTN groups. Group 2 was treated with L-NAME （40 mg kgI per day） in drinking water for 4 weeks. Group 3 received sildenafil （1.5 mg kg^-1 per day, by oral gavage） concomitantly with L-NAME. The prostatic portion of the VD was subjected to electrical field stimulation （EFS, 1-20 Hz）, and the P2X1 agonist α,β-methylene ATP （α,β meATP, 100 μmol L^-1-1 μmol L-1） and the al-adrenoceptor agonist phenylephrine （Phe, 100 μmol L^-1-1 mmol L^-1） were used to construct concentration-response curves. These experiments were repeated in the presence of P2X receptor antagonist, pyridoxalphosphate-6-azophenyl-2＇,4＇-disulfonic acid （PPADS, 30 μmol L-1）. VD contractions in response to EFS, a,β-meATP and Phe were significantly enhanced by L-NAME. Sildenafil treatment in the L-NAME group improved the contractile response of VD to EFS （20 Hz）. In the presence of PPADS, the enhanced contractile response of VD to EFS and a,β-meATP in hypertensive rats was reversed. In the rat model of chronic NO depletion, the purinergic and adrenergic components and EFS affect VD contractility. The VD contractile response may be mediated more by the purinergic system than the adrenergic system, and sildenafil may alter the ejaculatory response in men with PE.