Characterization of erectile function in monocrotaline-treated pulmonary hypertensive rats.
The aim of this study was to evaluate erectile function in monocrotaline (MCT)-treated rats with pulmonary hypertension (PH). Forty rats were divided into control (n = 20) and MCT-treated (n = 20) groups. Rats were treated with MCT (60 mg/kg subcutaneously) for 3 weeks to induce PH. Mean pulmonary arterial pressure (mPAP), medial hypertrophy index (percentage of wall thickness of pulmonary artery), and right ventricular hypertrophy (ratio of right ventricle [RV] to left ventricle + septum weight) were evaluated. In vivo erectile responses were assessed by measurement of intracavernosal pressure (ICP)/mean arterial pressure and total ICP (area under the curve). In vitro organ bath studies with corpus cavernosum smooth muscle strips were performed under both normoxic (95% O(2)/5% CO(2)) and hypoxic (by changing gas mixture to 95% N(2)/5% CO(2)) conditions. Erectile tissue was processed for immunohistochemistry. The MCT-treated group was associated with an increase in mPAP, medial hypertrophy index, and RV hypertrophy. MCT-induced PH rats had significantly reduced erectile responses compared with controls. Nitrergic, endothelium-dependent relaxations, as well as alpha-adrenergic contractile responses were significantly reduced in the corpus cavernosum of MCT rats. The functional responses during prolonged periods of hypoxia were similar to those observed in MCT-treated tissues. PH rats showed enhanced inducible nitric oxide synthase (NOS) protein localization, but endothelial NOS and neuronal NOS were unchanged. These results suggest changes in cavernosal physiology are caused by MCT acting on the penile tissues and the systemic vasculature.
Gur
Serap
S
Departments of Urology and Pharmacology, Pulmonary and Critical Care Medicine, Tulane Health Sciences Center, New Orleans, Louisiana 70112, USA.
Kadowitz
Philip J
PJ
Thammasitboon
Supat
S
Lasky
Joseph A
JA
Hellstrom
Wayne J G
WJ
D000818:Animals; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline / Q000494:pharmacology*; D010410:Penile Erection / Q000187:drug effects*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016686:Monocrotaline