Functional Properties of Suburothelial Microvessels in the Rat Bladder

Purpose: We investigated the properties of suburothelial microvessels, which have a vital role in maintaining microcirculation to cells involved in bladder afferent signaling. Materials and Methods: Changes in the diameter of rat bladder suburothelial microvessels were measured using video microscopy. Membrane potential changes and intracellular Ca2+ dynamics of suburothelial venules were examined using intracellular recording techniques and Ca2+ imaging of fluo-4 fluorescence, respectively. Results: Suburothelial venules showed spontaneous action potential and vasoconstriction activity while suburothelial arterioles were quiescent. Venular vasoconstriction was prevented by cyclopiazonic acid or nicardipine and decreased by 2-aminoethoxydiphenyl borate, niflumic acid or 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid. Venular smooth muscle cells and perivascular interstitial cells showed spontaneous Ca2+ transients. Nicardipine decreased the amplitude and disrupted the synchronicity of Ca2+ transients in and between the 2 cell populations. Residual Ca2+ transients in nicardipine occurred asynchronously and were abolished by cyclopiazonic acid. Suburothelial arterioles constricted in response to transmural nerve stimulation. These nerve induced constrictions were suppressed by prazosin or the selective alpha(1A) blocker RS17053 but not by the alpha(1D) blocker BMY7378. Remaining constrictions were abolished by guanethidine. Conclusions: Spontaneous vasoconstriction of suburothelial venules appears to result upon Ca2+ release from the sarcoplasmic reticulum upon activation of inositol 1,4,5-trisphosphate receptors. This Ca2+ opens Ca2+ activated Cl- channels to trigger action potentials and Ca2+ influx through L-type Ca2+ channels. Adjacent perivascular interstitial cells may also have a role in generating this spontaneous venular vasoconstriction. In contrast, sympathetic nerve released noradrenaline acts on alpha(1A)-adrenoceptors to constrict suburothelial arterioles.