Role of nitric oxide and Zaprinast a phosphodiesterase inhibitior in the modulation of human ureteral smooth muscle tone in vitro.

Aim of the study: To assess the role of nitric oxide (NO) and its second me ssenger, cGMP, on the mechanisms underlying human ureteral smooth muscle re laxation. Methods: Proximal segments of ureter were dissected form nephrectomy, then cut into rings and suspended in organ chambers. Isometric tone was recorded at baseline and after preincubation with KCl (120 mu mol). The Increasing concentration (10-8 - 10-4 M) of NO donors, Sodium nitroprusside, (SNP) and molsidomine (SIN-1) and a type V phosphodiesterase inhibitor, Zaprinast we re added to the organ chambers and a dose response curve was constructed fr om each experiment. Results: Dose-dependent relaxation was seen with all compounds. This was, h owever, more pronounced with SNP as compared with SIN-1. Zaprinast alone ha d marginal relaxant effect but markedly potentiated the relaxing effect of the NO donor SNP (p < 0.05). Inhibition of NO synthesis by the arginine ana logue L-NA increased electrical-induced contraction (98 +/- 4% vs 122+/-3%, p < 0.001). Conclusion: Activation of the soluble guanylate cyclase by NO donors marked ly relaxed significantly human ureteral smooth muscle but inhibition of pho sphodiesterase did not affect the in vitro relaxation. Our results suggest that cGMP is an important second messenger in the transduction signalling p athway leading to relaxation of human ureteral smooth muscle. By contrast, basal activity of phosphodiesterase seems to be marginal under physiologica l condition.