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

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 α,β-methylene ATP (α,β-meATP, 100 μmol L -1 -1 μmol L -1 ) and the α1-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, α,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 α,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.

Regulation of nerve-evoked contractions of rabbit vas deferens by acetylcholine

“…Studies by Gur et al. (2010) and da Silva et al. (2012) showed that EFS-evoked contractions of rat vas deferens were enhanced by the nitric oxide (NO) synthase inhibitor l -NAME, indicating an inhibitory role for NO in the rat vas deferens.…”

“…We speculated that one potential reason for this could be that EFS also activates an inhibitory pathway that opposes contraction, such that in the absence of the excitatory Ach effects, this inhibitory effect dominates. Studies by Gur et al (2010) and da Silva et al (2012) showed that EFS-evoked contractions of rat vas deferens were enhanced by the nitric oxide (NO) synthase inhibitor L-NAME, indicating an inhibitory role for NO in the rat vas deferens. NO is known to relax smooth muscle by activating the enzyme soluble guanylate cyclase (sGC).…”

“…For example, some investigators found that both the purinergic and adrenergic components of EFS-evoked contractions of rat vas deferens were enhanced by the NO synthase inhibitor l -NAME, indicating an inhibitory role for NO in the EFS response (Gur et al. 2010; da Silva et al. 2012).…”

“…The precise role of NO in the vas deferens is still unclear. For example, some investigators found that both the purinergic and adrenergic components of EFS-evoked contractions of rat vas deferens were enhanced by the NO synthase inhibitor L-NAME, indicating an inhibitory role for NO in the EFS response (Gur et al 2010;da Silva et al 2012). In contrast, (Postorino et al 1998;Nakanishi et al 2006) reported that NO facilitates sympathetic neurotransmission in rat and guinea-pig vas deferens rather than inhibiting it.…”

Physiological and pharmacological aspects of the vas deferens—an update

“…In an attempt to understand the influence of acute ischemia, models of torsion using rats have demonstrated a decrease in contractile response in the ipsilateral vas deferens (Karacay et al, 2011) Interestingly, spontaneous hypertensive rats have shown an INCREASE in contractile response to EFS and NA (Katsuragi et al, 1991), and Gur et al (2010) showed increased contractile respone to purinergic stimulation in L-NG-Nitroarginine Methyl Ester (L-NAME) induced hypertensive rat vas deferens. In conjuction with this study, Gur et al (2010) also demonstrated that rats co-treated with sildenafil and L-NAME reversed this EFS and α−β-methylATP hypercontractile property of the vas deferens. Additionally, a varicocele model has resulted in a decrease vas contractile response (Ozen et al, 2007).…”