| First Author | Tanaka H | Year | 2021 |
| Journal | Br J Pharmacol | Volume | 178 |
| Issue | 5 | Pages | 1073-1094 |
| PubMed ID | 33314051 | Mgi Jnum | J:346901 |
| Mgi Id | MGI:7616601 | Doi | 10.1111/bph.15342 |
| Citation | Tanaka H, et al. (2021) NO-mediated signal transmission in bladder vasculature as a therapeutic target of PDE5 inhibitors. Rodent model studies. Br J Pharmacol 178(5):1073-1094 |
| abstractText | BACKGROUND AND PURPOSE: While the bladder vasculature is considered as a target of PDE5 inhibitors to improve bladder storage dysfunctions, its characteristics are largely unknown. Thus, the functional and morphological properties of arteries/arterioles of the bladder focusing on the NO-mediated signal transmission were explored. EXPERIMENTAL APPROACH: Diameter changes in rat bladder arteries/arterioles were measured using a video-tracking system. Intercellular Ca(2+) dynamics in pericytes or smooth muscle cells (SMCs) of suburothelial arterioles were visualised using transgenic mice expressing GCaMP6 under control of the NG2- or parvalbumin-promoter. The perivascular innervation was investigated using fluorescence immunohistochemistry. KEY RESULTS: In rat suburothelial arterioles and vesical arteries, tadalafil (100 nM) attenuated nerve-evoked sympathetic vasoconstrictions. In both vascular segments, tadalafil-induced inhibition of sympathetic vasoconstriction was prevented by N omega-propyl-l-arginine hydrochloride (l-NPA, 1 muM), an nNOS inhibitor or N omega-nitro-l-arginine (l-NA, 100 muM). Both vascular segments were densely innervated with nNOS-positive nitrergic nerves in close apposition to tyrosine hydroxylase-immunoreactive sympathetic nerves. In pericyte-covered pre-capillary arterioles of the mouse bladder where sympathetic nerves were absent, nerve stimulation evoked transient reductions in pericyte Ca(2+) levels that were shortened by l-NPA and abolished by l-NA. In SMC-containing arterioles, tadalafil (10 nM) caused a l-NPA-sensitive suppression of sympathetic Ca(2+) transients. In mice, nitrergic perivascular nerves were distributed in the arterioles and the pre-capillary arterioles. CONCLUSION AND IMPLICATIONS: Both nitrergic nerve and nerve-evoked endothelial NO release appear to be involved in vasodilatory signal transmission in bladder vasculature. The NO-mediated signal transmission is a potential target for PDE5 inhibitor therapy in bladder dysfunctions. |
