Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide-phosphodiesterase type 5-cyclic guanosine 3',5'-monophosphate pathway.
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.
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.
Yukihito
Y
Higashi
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000502:physiology; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology; D001341:Autonomic Nervous System / Q000503:physiopathology; D002318:Cardiovascular Diseases / Q000503:physiopathology*; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5 / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D006801:Humans; D059411:Lower Urinary Tract Symptoms / Q000503:physiopathology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009569:Nitric Oxide / Q000502:physiology*; D011470:Prostatic Hyperplasia / Q000503:physiopathology*; D051381:Rats; D012307:Risk Factors; D015398:Signal Transduction; D014652:Vascular Diseases / Q000503:physiopathology; D054460:rho-Associated Kinases / Q000502:physiology; D020742:rhoA GTP-Binding Protein / Q000502:physiology
C066737:RHOA protein, human; D009569:Nitric Oxide; D054460:rho-Associated Kinases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; D054706:Cyclic Nucleotide Phosphodiesterases, Type 5; D020742:rhoA GTP-Binding Protein
benign prostatic hypertrophy; lower urinary tract symptoms; nitric oxide; phosphodiesterase type 5-cyclic guanosine 3′,5′-monophosphate; vascular function