Lower urinary tract symptoms/benign prostatic hypertrophy and vascular function: Role of the nitric oxide–phosphodiesterase type 5–cyclic guanosine 3′,5′‐monophosphate pathway

Abstract

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 0 ,5 0 -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 0 ,5 0 -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 0 ,5 0 -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 oxidecyclic guanosine 3 0 ,5 0 -monophosphate pathway, vascular function and cardiovascular outcomes are examined.Key words: benign prostatic hypertrophy, lower urinary tract symptoms, nitric oxide, phosphodiesterase type 5-cyclic guanosine 3 0 ,5 0 -monophosphate, vascular function.

Vascular Pathways of Testosterone: Clinical Implications

“…Regarding the vascular endothelium, the key contributor to the androgen vasorelaxation effect is controversial. Some studies demonstrated that vascular endothelium has a major role in the T vasodilator mechanism [26,27], depending on species and gender. On the contrary, others demonstrated that this effect may occur through an independent-endothelium pathway [28][29][30], by direct action of T on the vascular smooth muscle.…”

Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation

“…Similar to TRP channels, the activation of mechanosensitive channels such as Piezo1 114 can also result in enhanced microglial migration (Fig. 2) via cytoskeleton remodeling [116][117][118][119][120] .…”

Urine Mir-21-5P As a Potential Biomarker for Predicting Effectiveness of Tadalafil in Benign Prostatic Hyperplasia

“…The PDE5-Is have been reported to exert strong pharmaceutical effects for smooth muscle relaxant in bladder neck and prostatic urethra [ 9 , 18 , 19 ], vasodilatation response in lower urinary tract (LUT) [ 7 , 20 ], inhibition of bladder afferent nerve activity [ 21 ] and reduction in prostatic inflammation related with LUTS [ 8 ]. Although the functional role of PDE5 remains controversial, a main stream is NO/cGMP signaling pathway in the crosstalk between efferent nerve terminal and LUT smooth muscle cell, or endothelial and vessel smooth muscle cell [ 22 ]. Previous reports revealed that expression of PDE5 is robust in endothelial and smooth muscle cells of LUT vessels, and tadalafil plays a critical role in vasodilatation of vesicular-differential artery via inhibition of cGMP degradation by blocking of PDE5 activity [ 6 , 23 ].…”