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

Introduction. The physiological significance of the l-arginine-nitric oxide (NO)-cGMP pathway in the regulation of smooth muscle tone in various organs of the human genitourinary tract, such as the corpus cavernosum, prostate, ureter and urethra, has been fairly well established. Nevertheless, there is sparse information on the relevance of the NO-mediated signal transduction cascade in the functional control of mammalian seminal vesicles. reported the distribution of endothelial and neuronal nitric oxide synthase (eNOS and nNOS) in the cellular anatomy of the human seminal vesicles (SV) and evaluated the effects of some NO-donating agents on the adrenergic tension of isolated SV strip preparations. The aim of the present study was to evaluate the effects of the NO-donating drugs sodium nitroprusside (NNP), GSNO, SNACET and linsidomine (SIN-1, CORVASAL^®) as well as the adenylate cyclase stimulating agent forskolin on electrically induced contractions and on the tissue levels of the cyclic nucleotide monophosphates cGMP and cAMP of isolated human seminal vesicle strip preparations.

Materials and methods. SV tissue strip preparations were applied to an organ bath system and maintained under standard conditions. Phasic contractile activity was induced by means of electrical field stimulation (frequency 80 Hz, single pulse 1 ms, pulse duration 1 s, interval 120 s, amplitude 10 V). After stable contraction amplitudes had been reached, the drugs were added to the bath chambers in a cumulative manner (10⁹-10⁵ m) and isometric responses of the tissue were registered. Following time- and dose-dependent drug exposition to the tissue strips, clamp-freezing, tissue homogenization and extraction of cyclic nucleotides, cAMP and cGMP were measured using enzyme immunoassays (ELISA, supplied by Institut fur Hormonforschung, Hamburg, Germany).

Results. EFS-induced amplitudes were dose-dependently attenuated by the drugs. The following rank order of potency was obtained: GSNO > NNP > Forskolin > SNACET ≤ SIN-1. The relaxing effect of GSNO was effectively antagonized in the presence of guanylate cyclase inhibitor methylen blue (10 µm). The inhibitory effects of GSNO, NNP and forskolin on contractile activity were paralleled by an increase in tissue cGMP (2- to 100-fold) and cAMP (7- to 9-fold), respectively.

Conclusion. Our results strongly support the hypothesis that the praesynaptically induced motility of human seminal vesicles is in part regulated by the NO-cGMP cascade. This may provide a rationale for the use of NO donors in the pharmacotherapy of ejaculatory dysfunction due to hyperexcitation.