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

Gur, S; Sikka, SC; Knight, GE; Burnstock, G; Hellstrom, WJG; (2010) Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension: effect of sildenafil. ASIAN J ANDROL , 12 (3) 415 - 421. 10.1038/aja.2009.70.

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Abstract

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 kg(-1) 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 P2X(1) agonist alpha,beta-methylene ATP (alpha,beta-meATP, 100 mu mol L-1-1 mu mol L-1) and the alpha 1-adrenoceptor agonist phenylephrine (Phe, 100 mu mol 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 mu mol L-1). VD contractions in response to EFS, alpha,beta-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 alpha,beta-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.

Type:Article
Title:Purinergic contraction of the rat vas deferens in L-NAME-induced hypertension: effect of sildenafil
DOI:10.1038/aja.2009.70
Keywords:hypertensive rat, NG-nitro-L-arginine methyl ester, purinergic receptors, P2X, sildenafil, vas deferens, ERECTILE DYSFUNCTION, POSSIBLE MECHANISMS, GUINEA-PIG, ATP, NORADRENALINE, RECEPTORS, NEUROTRANSMISSION, EJACULATION, STIMULATION, BINDING
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Life Sciences > Biosciences (Division of)

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