The nitric oxide pathway in pig isolated calyceal smooth muscle

In pig and humans, whose kidneys have a multi-calyceal collecting system, t he initiation of ureteral peristalsis takes place in the renal calyces. In the pig and human ureter, recent evidence suggests that nitric bride (NO) i s an inhibitory mediator that may be involved in the regulation of peristal sis. This study was designed to assess whether the NO synthase/NO/cyclic GM P pathway modulates the motility of pig isolated calyceal smooth muscle. Im munohistochemistry revealed a moderate overall innervation of the smooth mu scle layer, and no neuronal or inducible NO synthase (NOS) immunoreactiviti es. Endothelial NOS immunoreactivities were observed in the urothelium and vascular endothelium, and numerous cyclic GMP-immunoreactive (-IR) calyceal smooth muscle cells were found. As measured by monitoring the conversion o f L-arginine to L-citrulline, Ca2+-dependent NOS activity was moderate. Ass essment of functional effects was performed in tissue baths and showed that NO and SIN-1 decreased spontaneous and induced contractions of isolated pr eparations in a concentration-dependent manner. In strips exposed to NO, th ere was a 10-fold increase of the cyclic GMP levels compared with control p reparations (P < 0.01). It is concluded that a non-neuronal NOS/NO/cyclic G MP pathway is present in pig calyces, where it may influence motility. The demonstration of cyclic GMP-IR smooth muscle cells suggests that NO acts di rectly on these cells. This NOS/NO/cyclic GMP pathway may be a target for d rugs inhibiting peristalsis of mammalian upper urinary tract. (C) 1999 Wile y-Liss, Inc.