Cardiovascular risk factors have been shown to be correlated with impaired sexual function

Cardiovascular risk factors have been shown to be correlated with impaired sexual function. for isometric pressure measurement. The contraction induced by alpha-adrenergic agonist phenylephrine, and the relaxation induced from the nitric oxide (NO) donor sodium nitroprusside (SNP) and by the Rho-kinase inhibitor Y-27632 were performed in the absence and in the presence of the nitric oxide synthase (NOS) inhibitor L-NNA. Results Changes in ICP/MAP induced by ganglionic activation were not different between 2K-1C and SHAM rats. The contractile response induced by phenylephrine as well as the relaxation induced by SNP or the Y-27632 were related in cavernosal pieces from both organizations. However, in the presence of L-NNA, the relaxation induced by Y-27632 was significantly impaired in 2K-1C compared to SHAM). Conclusions These data suggest that hypertension and ED could be dissociated from high levels of blood pressure in some animal models of hypertension. Erectile function in 2K-1C hypertensive rats is definitely maintained in spite of the improved Rho-kinase activity by improved NO signaling. for 6 weeks when erectile function and isolated cavernosal contractility studies were performed. Systolic blood pressure (SBP) was MK-571 measured weekly by tail-cuff, and the animals were regarded as hypertensive if SBP was higher than 160 mmHg at the end of 6th week of implantation of the MK-571 metallic clip or sham surgery. All procedures were conducted in accordance with the Medical College of Georgia’s Animal Use for Study and Education Committee. In Vivo Measurement of Erectile Reactions To compare the erectile function of 2K-1C hypertensive with SHAM normotensive rats, the model of erection in anesthetized animals was used. Rats were anesthetized by ketamine/xylazine and managed on supplemental doses as needed. Mean Rabbit Polyclonal to C1S arterial pressure (MAP) and intracavernosal pressure (ICP) were continuously and simultaneously monitored as previously described.5 Briefly, the remaining carotid artery was cannulated for MAP recording. To monitor ICP, the shaft of the penis was denuded of pores and skin and fascia, and a 30-gauge needle was MK-571 put into the right corpus cavernosum. The abdominal cavity was opened, exposing the major pelvic ganglion (MPG). Bipolar electrodes connected to a Grass stimulator (Astro-Med, USA) were positioned on the MPG. Electrical activation of the MPG (5-ms pulse, 30 s, 12 Hz) at different voltages (1 to 5 V) was performed. All pressure data were collected for analysis using a PowerLab/8SPTM data acquisition system. Isometric Force Generation in Cavernosal Pieces Under pentobarbital anesthesia (50 mg/Kg, i.p.), rats were killed by pneumothorax and the penis was excised, as previously explained.5 After removal of the ventral corpus spongiosum, dorsal vein and surrounding connective tissue, the right and remaining corpora cavernosa were obtained. Each strip was longitudinally mounted in an organ chamber for isometric pressure recordings and bathed in physiological salt MK-571 remedy (PSS) of the following composition in mM: NaCl 130.0, KCl 4.7, KH2PO4 1.2, MgSO4 1.2, CaCl2 1.6, NaHCO3 14.9, EDTA 0.03 and glucose 5.5, which was maintained at 37C and bubbled with 95% O2 and 5% CO2. Cavernosal pieces were stretched to 300 mg passive tension and changes in isometric push were recorded using a PowerLab/8SPTM data acquisition system (AD Tools, USA). After 1-hour equilibration period in the presence of indomethacin (10-5M) the contractility studies were performed. Cavernosal clean muscle mass contraction to alpha adrenergic receptor activation was tested through concentration-responses curves to phenylephrine (10-7 to 310-4M). NO-dependent relaxation was evaluated via concentration-response curves to sodium nitroprusside (SNP, 10-8 to 10-4M) in pieces previously contracted by phenylephrine (10-5M). Rho-kinase signaling and/or nitric oxide formation were compared through relaxation curves to a Rho-kinase inhibitor (Y-27632, 10-8 to 10-5M), performed in pieces contracted by phenylephrine (10-5M), either in the absence or in the presence of a NOS inhibitor [N-nitro-L-arginine (L-NNA), 10-4M]. The cavenosal pieces weight/length percentage from SHAM and 2K-1C rats were similar (data not demonstrated). Each strip was only used once for a single EFS or drug-induced relaxation. Medicines Indomethacin, phenylephrine, sodium nitroprusside (SNP), and N-nitro-L-arginine (L-NNA) were purchased from Sigma Chemicals, USA. The Y-27632 compound [(R)-(+)-trans-N-(4-pyridyl)-4-(1-aminoethyl)-cyclohexanecarboxamide] was from Calbiochem, USA. Statistics The data are indicated as imply (SEM). Single comparisons between organizations (SBP and – LogEC50 were performed using two-tailed unpaired test. Multiple comparisons among groups were analyzed by one-way ANOVA followed by post hoc Student-Newman-Keuls checks. Differences were regarded as significant at 5.630.07, Figure 3A). L-NNA experienced no significant effect on Y-27632-induced relaxation in corpus cavernosum from SHAM rats (-LogEC50 5.630.07 and 5.490.06, control L-NNA treated, Number 3B). On the other hand, L-NNA treatment significantly inhibited Y-27632-induced relaxation in 2K-1C rat cavernosal clean muscle mass (-LogEC50 5.840.10 and 5.430.03, control L-NNA treated p 0.05, Figure 3C). Open in a separate window Number 3 A. Y-27632-induced relaxation (% of the phenylephrine contraction) of cavernosal pieces from 2K-1C and SHAM rats. B. Y-27632-induced relaxation (% of the phenylephrine contraction) in the absence and in the presence.