NO-mediated signal transmission in bladder vasculature as a therapeutic target of PDE5 inhibitors. Rodent model studies

Autor: Hidekazu, Tanaka, Retsu, Mitsui, Mitsuhiro, Oishi, Stefan, Passlick, Ronald, Jabs, Christian, Steinhäuser, Kenji F, Tanaka, Hikaru, Hashitani
Rok vydání: 2020
Předmět:
Zdroj: British journal of pharmacologyREFERENCES. 178(5)
ISSN: 1476-5381
Popis: 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.Diameter changes in rat bladder arteries/arterioles were measured using a video-tracking system. Intercellular CaIn 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 ω-propyl-l-arginine hydrochloride (l-NPA, 1 μM), an nNOS inhibitor or N ω-nitro-l-arginine (l-NA, 100 μM). 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 CaBoth 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.
Databáze: OpenAIRE