Localization of constitutive nitric oxide synthase isoforms and the nitricoxide target enzyme soluble guanylyl cyclase in the human bladder

Purpose: Nitric oxide is a free radical gas synthesized from L-arginine by a family of isoenzymes called nitric oxide synthase that has an important r ole in smooth muscle relaxation. L-arginine, the substrate for nitric. oxid e synthase, may be beneficial under pathophysiological conditions in the bl adder, as in interstitial cystitis. We determined the localization of nitri c oxide synthase and the target enzyme of NO, soluble guanylyl cyclase, in the human bladder. Materials and Methods: Benign bladder tissues were obtained from 18 patient s with localized superficial bladder tumors undergoing transurethral bladde r resection. Histochemical nicotinamide adenine dinucleotide phosphate-diap horase staining, nitric oxide synthase immunohistochemical testing and solu ble guanylyl cyclase immunoreactivity studies were performed in all benign tissue specimens. Results: A different pattern of nitric oxide synthase expression was confir med by nicotinamide adenine dinucleotide phosphate-diaphorase staining and immunohistochemical testing for endothelial and neuronal nitric oxide synth ase. In addition to endothelial nitric oxide synthase expression, detrusor smooth muscle was recognized as an important location of endothelial nitric oxide synthase, while the urothelium had only small endothelial nitric oxi de synthase positive cell clusters. Neuronal nitric oxide synthase expressi on was only found in nitrinergic fibers of the submucosal surface and betwe en muscle cells. Detrusor and vascular smooth muscle as well as interstitia l cells, nerve fibers and transitional epithelium were recognized as target s of nitric oxide, as shown by soluble guanylyl cyclase expression. Conclusions: The distribution of constitutive nitric oxide synthase isoform s and soluble guanylyl cyclase provides evidence of nitric oxide-cyclic gua nosine monophosphate mediated regulation of detrusor smooth muscle relaxati on, neurotransmission and blood flow. Furthermore, the urothelium may also be a target of nitric oxide.