THE L-ARGININE NITRIC-OXIDE CYCLIC-GMP PATHWAY MEDIATES INHIBITORY NONADRENERGIC-NONCHOLINERGIC NEUROTRANSMISSION IN THE CORPUS CAVERNOSUM OF HUMAN AND RABBIT

The objective of this study was to compare the effects of nonadrenergi c-noncholinergic (NANC) stimulation and nitric oxide (NO) on isolated strips of corpus cavernosum from human and rabbit penis. Authentic NO and electrical field stimulation (EFS) caused rapid, marked, and trans ient endothelium-independent relaxation responses associated with tiss ue cGMP and nitrite (NO2-) accumulation. Responses to both EFS and NO were enhanced by M&B 22,948 and inhibited by oxyhemoglobin or methylen e blue. Responses to EFS were inhibited by NO-synthase inhibitors. The subcellular sites of NO generation after EFS or nitroglycerin compare d with acetylcholine were less accessible to added oxyhemoglobin, thus supporting the view that NO is generated in NANC neurons or innervate d smooth muscle. NO-synthase from corpus cavernosum is a constitutive cytosolic isoform that is dependent on nicotinamide adenine dinucleoti de phosphate and tetrahydrobiopterin and is activated by calcium calmo dulin.