An in vitro investigation of aorta and corpus cavernosum from eNOS and nNOS gene-deficient mice (original) (raw)

In order to ascertain the relative contribution of the endothelial and neuronal nitric oxide (NO) synthase isoforms on NO-dependent vascular and nerve function in vitro, aorta and corpus cavernosum from mice deficient in their expression (eNOS−/− and nNOS−/−) were isolated in organ baths for tension measurements. Agonist or electrical field stimulation (EFS) evoked nerve-mediated responses were compared against wild-type controls. In aortas from nNOS−/− mice, contraction responses to phenylephrine were increased. Conversely, endotheliumdependent relaxation (EDR) to acetylcholine (ACh) was decreased. In contrast, eNOS−/− aortas showed decreased sensitivity to phenylephrine and developed a flurbiprofensensitive contraction to ACh, and sensitivity to the NOdonor sodium nitroprusside was increased. In cavernosum from eNOS−/− and nNOS−/− mice, maximum contractions to phenylephrine and EFS, and relaxation responses to nitroprusside, were increased. As in aorta, ACh addition led to a contractile response in eNOS−/− cavernosum. Maximum EFS induced non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxation was increased in eNOS−/−, whilst being decreased in nNOS−/− cavernosum. These data suggest that whilst NO-dependent vascular function is primarily eNOS mediated, and nerve function nNOS mediated, aorta function may be at least partially reliant on nNOS-related mechanisms. In addition, mechanisms of physiological compensation were observed, which require further study.