Effects of various nitric oxide donating agents on the contractility and cyclic nucleotide turnover of human seminal vesicles in vitro

Objectives. To evaluate the effects of the nitric oxide (NO)-donating drugs sodium nitroprusside, S-nitroso-glutathione (GSNO), S-nitroso-N-acetylcysteineetylester (SNACET), and linsidomine (SIN-1), as well as the adenylyl cyclase-stimulating agent forskolin, on electrically induced contractions and on tissue levels of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) of isolated human seminal vesicle strip preparations. The significance of the L-arginine-NO-cGMP pathway in the regulation of smooth muscle tone in the human genitourinary tract has been well established; however, information on the relevance of NO-mediated signal transduction in the functional control of mammalian seminal vesicles is still sparse. Methods. Seminal vesicle strip preparations were applied to an organ bath system under standard conditions. Phasic contractions were induced by electrical field stimulation (frequency 80 Hz, amplitude 10 V, single pulse 1 ms, total pulse duration 1 second, pause 90 seconds). After stable contraction amplitudes had been reached, the drugs were added in a cumulative manner (0.001 to 10 AM), and the isometric responses were registered. After drug exposure, freezing, tissue homogenization, and extraction of cyclic nucleotides, cAMP and cGMP were measured by means of enzyme-linked immunosorbent assays. Results. Electrical field stimulation-induced amplitudes were attenuated by the drugs in a dose-dependent manner. The rank order of potency was GSNO > sodium nitroprusside > forskolin > SNACET : SIN-1. The relaxing effect of GSNO was antagonized in the presence of 10 muM of guanylyl cyclase inhibitor methylene blue. The inhibitory effects of GSNO, sodium nitroprusside, and forskolin on the contractile activity were paralleled by an increase in tissue cGMP (2 to 100-fold) and cAMP (7 to 9-fold). Conclusions. Our results strongly support the hypothesis that the contractility of human seminal vesicles is in part regulated by the NO-cGMP-cascade. This may give a rationale for the use of S-nitrosothiols, such as GSNO, in the pharmacotherapy of hyperexcitatory disturbances of ejaculation, (C) 2002, Elsevier Science Inc.