Higashi Yukihito
Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University Hospital, Hiroshima, Japan.
Divivsion of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.
Int J Urol. 2017 Jun;24(6):412-424. doi: 10.1111/iju.13336. Epub 2017 Mar 22.
It is well known that there is an association of lower urinary tract symptoms/benign prostatic hypertrophy with cardiovascular disease, suggesting that lower urinary tract symptoms/benign prostatic hypertrophy is a risk factor for cardiovascular events. Vascular function, including endothelial function and vascular smooth muscle function, is involved in the pathogenesis, maintenance and development of atherosclerosis, leading to cardiovascular events. Vascular dysfunction per se should also contribute to lower urinary tract symptoms/benign prostatic hypertrophy. Both lower urinary tract symptoms/benign prostatic hypertrophy and vascular dysfunction have cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes mellitus, aging, obesity and smoking. Inactivation of the phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate-nitric oxide pathway causes lower urinary tract symptoms/benign prostatic hypertrophy through an enhancement of sympathetic nervous activity, endothelial dysfunction, increase in Rho-associated kinase activity and vasoconstriction, and decrease in blood flow of pelvic viscera. Both endogenous nitric oxide and exogenous nitric oxide act as vasodilators on vascular smooth muscle cells through an increase in the content of cyclic guanosine 3',5'-monophosphate, which is inactivated by phosphodiesterase type 5. In a clinical setting, phosphodiesterase type 5 inhibitors are widely used in patients with lower urinary tract symptoms/benign prostatic hypertrophy. Phosphodiesterase type 5 inhibitors might have beneficial effects on vascular function through not only inhibition of cyclic guanosine 3',5'-monophosphate degradation, but also increases in testosterone levels and nitric oxide bioavailability, increase in the number and improvement of the function of endothelial progenitor cells, and decrease in insulin resistance. In the present review, the relationships between lower urinary tract symptoms/benign prostatic hypertrophy, the phosphodiesterase type 5-nitric oxide-cyclic guanosine 3',5'-monophosphate pathway, vascular function and cardiovascular outcomes are examined.
众所周知，下尿路症状/良性前列腺增生与心血管疾病相关，这表明下尿路症状/良性前列腺增生是心血管事件的一个危险因素。血管功能，包括内皮功能和血管平滑肌功能，参与动脉粥样硬化的发病机制、维持和发展，进而导致心血管事件。血管功能障碍本身也应导致下尿路症状/良性前列腺增生。下尿路症状/良性前列腺增生和血管功能障碍都有心血管危险因素，如高血压、血脂异常、糖尿病、衰老、肥胖和吸烟。5型磷酸二酯酶-环磷酸鸟苷-一氧化氮途径的失活通过增强交感神经活动、内皮功能障碍、Rho相关激酶活性增加和血管收缩以及盆腔脏器血流减少导致下尿路症状/良性前列腺增生。内源性一氧化氮和外源性一氧化氮都通过增加环磷酸鸟苷的含量对血管平滑肌细胞起血管舒张作用，而环磷酸鸟苷被5型磷酸二酯酶灭活。在临床环境中，5型磷酸二酯酶抑制剂广泛用于下尿路症状/良性前列腺增生患者。5型磷酸二酯酶抑制剂可能不仅通过抑制环磷酸鸟苷降解，还通过提高睾酮水平和一氧化氮生物利用度、增加内皮祖细胞数量和改善其功能以及降低胰岛素抵抗，对血管功能产生有益影响。在本综述中，研究了下尿路症状/良性前列腺增生、5型磷酸二酯酶-一氧化氮-环磷酸鸟苷途径、血管功能和心血管结局之间的关系。
