Effect of Metformin on the Expression of Nitric Oxide Synthase in High Fat Fed Obese Rats / 대한남성과학회지

PURPOSE: Obesity is a well known risk factorfor erectile dysfunction, and metformin normalizes androgen levels in patients with polycystic ovary syndrome and decreases body fat and leptin concentration in normal weight men. Thus, we hypothesized that metformin may restore the neuroendocrine abnormalities associated with obesity and improve erectile dysfunction. MATERIALS AND METHODS: Obesity was induced by a high fat(HF) diet fed for 4 months, and then metformin(300 mg/kg/day) was administered for 4 weeks. Penile nitric oxide synthase(NOS) expression and luteinizing hormone (LH), follicle stimulating hormone(FSH), testosterone, leptin, corticotropin releasing factor(CRF), adrenocorticotropin (ACTH), and proopiomelanocortin(POMC) were evaluated in control and HF obese rats. RESULTS: Penile nNOS and eNOS were suppressed markedly, and serum leptin and FSH were increased in HF rats compared to controls. However, POMCexpression in the hypothalamus was decreased in HF rats compared to controls,despite slightly elevated cerebrospinal fluid(CSF) leptin concentration. Metformin treatment for 4 weeks restored penile nNOS and eNOS expression, decreased serum leptin, increased POMC expression in the hypothalamus, and decreased serum concentration of FSH and CRF in HF rats. Surprisingly, metformin increased CSF leptin concentration in both control and HF rats. CONCLUSIONS: These results suggested that NOS expression was suppressed by the HF diet, but restored by metformin treatment. The effect of metformin on NOS expression resulted from not only a leptin sensitizing effect but also through a normalizing effect on levels of endocrine factors.

Effect of Nitric Oxide Donor on Penile Erection in Rats / 대한비뇨기과학회지

Nitric oxide (NO) is known to mediate penile erection by activating intracellular cyclic GMP pathway. It is also suggested that cGMP pathway, on penile erection, has dominant role over the other secondary messenger pathway with cAMP, etc. Based on the hyposthesis that activation of NO-cGMP pathway could represent a more physiologic and effective approach in the treatment of erectile dysfunction, several NO donors and activator of cGMP have been used in human and animal studies of impotence. However the efficacy of those remains debatable. In the present study, we investigated the effect of NO donor [linsidomine chlorhydrate (SIN-1), S-nitroso-N-acetylpcnicillamine (SNAP), sodium nitroprusside (SNP)] alone and in combination with zaprinast (cGMP specific phosphodiesterase inhibitor) on penile erection in rats. NO donors used in this study, except SNP, did not induce penile erection sufficiently. SNP-induced penile erection is comparable to the erection induced by cavernosal nerve stimulation. However, direct applicaion of SNP in the treatment of impotence may not be acceptable as it causes a marked hypotension. Zaprinast given intracayernously either alone or in combination with NO donor may not be clinically effective. Combination with zaprinast is not shown to enhance the effect of NO donor on penile erection. Therefore, combination of NO donor with other drugs modulating different pathway may be a therapeutic approach to erectile dysfunction worthy of further investigation.

Correlation of Cavernous Relaxation with Nitric Oxide Concentration in the Rabbit / 대한비뇨기과학회지

Nitric oxide (NO) is known to act as an important neural mediator of penile erection. However, the degree of penile erection related to the concentration of NO released from corpus cavernosum has not been known yet. The present study was undertaken to correlate the degree of relaxation of the corpus cavernosum with concentration of NO by treatment of various NO releasing agents. Isometric tension of the rabbit cavernous strips was measured by polygraph system. The concentration of NO released from the same strips was simultaneously measured using an electrochemical method (Iso NO meter), which allows to detect change of NO gas level in perfusate of the organ bath. The cumulative additions of endothelial dependent agents, both acetylcholine and bradykinin at concentration from 0.00000001 to 0.0001M relaxed the cavernous strips precontracted by 0.000001M phenylephrine in concentration-dependent manner, which were highly correlated with the concentration of NO (38.9 +/- 15.2 nM at 0.00000001M - 74.5 +/- 18.4 nM at 0.0001M of acetylcholine; 30.2 +/- 5.8 nM at 0.00000001M - 90.5 +/- 10.2 at 0.0001M of bradykinin) released from the same strips, Furthermore, 3-[(3-cholamido propyl)]-l-propane sulfonate (CHAPS), a deendothelial agent, markedly suppressed both acetylcholine or bradykinin-induced cavernous relaxation and abolished NO release. In contrast, endothelial independent agent such as sodium nitroprusside (SNP), N-ethoxycarbonyl-3-morpholino-sydonimine (SIN-l) and s-nitroso-N-acetylpenicillamine (SNAP) at concentration from 0.00000001 to 0.001M relaxed the cavernous strips in` concentration dependent manner, without altering the basal concentration of NO in perfusate. From these results, it appears that the degree of cavernous relaxation induced by acetylcholine or bradykinin is highly correlated with the concentration of NO released from the cavernous endothelium. Furthermore, the direct electrochemical measurement of NO concentration in perfusate may be useful for further NO research in association with penile erection.

Effect of Hybrid Laser Prostatectomy and Laser Thermotherapy on Benign Prostatic Hyperplasia / 대한비뇨기과학회지

Recently, laser treatment of benign prostatic hyperplasia (BPH) is considered as a promising alternative to traditional transurethral resection of the prostate (TURP). To evaluate the effectiveness and safety of laser therapy on BPH, we compared the results of transurethral balloon laser thermotherapy (TUBALT, n=13) and Hybrid laser prostatectomy (HLP, n=21) with those of TURP (n=25) in 58 patients with mild and moderate BPH. Following data were evaluated at postoperative 1, 3 and 6 months : AUA symptom score (SS), maximal flow rate (Qmax), subjective symptom improvement (SI), postoperative complications. All 3 groups show significant improvement after treatment in the Qmax values. Among 3 groups, the Qmax value was lower in TUBALT group (12.9+/-3.3 ml/sec) than those in HLP group (15.5+/-5.2 ml/sec) and TURP group (18.7+/-5.3 ml/sec) on postoperative 6 months. The Qmax values were not significantly different between HLP and TURP groups. In the SS values, all 3 groups show significant improvement after treatment and, TUBALT (9.9+/-9.7) and HLP (10.3+/-9.4) group were comparable to TURP group (5.2+/-4.2) on postoperative 6 months. In global assessment of SI, both HLP (87.5%) and TUBALT (75%) group were also comparable to TURP (90%) group on postoperative 3 months. but TUBALT group showed delayed symptom improvement compared to TURP group. Postoperative complications were minimal both in HLP and TUBALT groups, compared to TURP group. These results suggest that both HLP and TUBALT are effective in mild and moderate BPH, Further more, HLP treatment could be considered a promising alternative to TURP.