Mechanisms underlying spontaneous constrictions of postcapillary venules in the rat stomach

Postcapillary venules (PCVs) play a critical role in regulating capillary hydrostatic pressure, but their contractile mechanisms are not well understood. We examined the properties of spontaneous vasomotion and corresponding Ca(2+) transients in gastric PCV. In the rat gastric submucosa, changes in PCV diameter and intracellular Ca(2+) dynamics were visualised by video tracking system and fluorescent Ca(2+) imaging, respectively, while PCV morphology was examined by immunohistochemistry. Stellate-shaped PCV mural cells expressing α-smooth muscle actin exhibited synchronised spontaneous Ca(2+) transients to develop vasomotion which was abolished by nifedipine (1 μM), cyclopiazonic acid (10 μM), or Ca(2+)-activated Cl(-) channel inhibitors (100 μM niflumic acid, 1 μM T16Ainh-A01). A gap junction blocker (3 μM carbenoxolone) disrupted the synchrony of spontaneous Ca(2+) transients amongst PCV mural cells and attenuated spontaneous vasomotion. Low chloride solution ([Cl(-)]0 = 12.4 mM) also disrupted the synchrony of spontaneous Ca(2+) transients and abolished vasomotion. Na(+)-K(+)-Cl(-) co-transporter inhibitors (10 μM bumetanide, 30 μM furosemide) suppressed spontaneous Ca(2+) transients and vasoconstrictions. A phosphodiesterase type 5 (PDE5) inhibitor (1 μM tadalafil) disrupted the spontaneous Ca(2+) transient synchrony and abolished vasomotion in a nitric oxide (NO)-dependent manner. Thus, gastric PCVs exhibit spontaneous vasomotion, resulting from synchronised spontaneous Ca(2+) transients within a network of stellate-shaped PCV mural cells. An active Cl(-) accumulation partly via Na(+)-K(+)-Cl(-) co-transport appears to be fundamental in maintaining depolarisation upon the opening of Ca(2+)-activated Cl(-) channels that triggers Ca(2+) influx via voltage-dependent L-type Ca(2+) channels. Basal PDE5 activity may continuously counteract vaso-relaxing effects of endothelial NO to maintain spontaneous vasomotion.