Pravastatin improves the impaired nitric oxide-mediated neurogenic and endothelium-dependent relaxation of corpus cavernosum in aged rats

Abstract

Aim: The aim of this study was to investigate the effect of pravastatin treatment on diminished corpus cavernosum (CC) function associated with aging.

Methods: Male rats were divided into three groups as adult rats (12–14 weeks old), aged rats (72–80 weeks old) and aged rats given 10?mg/kg/d pravastatin in drinking water for six weeks. Blood pressure was measured by tail-cuff method. Total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides and testosterone levels were estimated in blood. Changes in expression levels of endothelial nitric oxide synthase (eNOS), phosphorylated eNOS (p-eNOS) (Ser-1177), neuronal nitric oxide synthase (nNOS), NADPH oxidase subunit gp91^phox, Rho A and Rho kinase (ROCK2) in CC were assessed by immunohistochemistry. Nitric oxide (NO)-mediated endothelium-dependent and neurogenic CC relaxation were evaluated by acetylcholine (ACh, 0.1?nM–100?µM) and electrical field stimulation (EFS; 30?V, 5?ms, 2–32?Hz), respectively.

Results: In aged rats, NO-mediated, both endothelium-dependent and neurogenic CC relaxation, were significantly impaired as compared to adult rats. Besides, eNOS, p-eNOS and nNOS expressions decreased significantly in CC from aged rats, while gp91^phox, RhoA and ROCK2 expressions increased significantly. The diminished relaxation in response to ACh or EFS as well as the changes in expression of these proteins in aged rats were significantly improved by pravastatin treatment.

Conclusion: Pravastatin improves NO-mediated CC relaxations of aged rats probably by inhibiting NADPH oxidase/Rho kinase pathways, and this effect does not seem to be associated with lipid lowering effect of this drug.     

阿昔莫司联合普伐他汀治疗老年混合型高脂血症的疗效与安全性

目的观察阿昔莫司联合普伐他汀治疗老年冠心病合并混合型高脂血症的疗效与安全性。方法2006年2月至2008年1月在中日友好医院高干医疗科诊断为冠心病合并混合型高脂血症的71例患者，年龄在60～75岁，其中分为阿昔莫司＋普伐他汀联合治疗组及单用普伐他汀治疗组，进行6个月的治疗随访。比较两组治疗前后的血脂水平、血脂达标率以及不良反应的发生情况。结果①6个月后，阿昔莫司＋普伐他汀联合组治疗TC、TG、LDL—C显著降低，HDL—C水平（P〈0．05）升高。而普伐他汀治疗TC、LDL—C水平显著降低，对TG、HDL—C影响不大。（④治疗6个月后，联合治疗组TC、LDL—C、HDL—C、TG的达标率分别为78.3％，75．7％，49．5％，59．4％，均高于普伐他汀组（P〈0．05）。结论阿昔莫司联合普伐他汀治疗老年冠心病合并混合型高脂血症的患者，可以全面改善患者的血脂谱，使血脂达标率明显提高，具有良好的安全性和耐受性。