Effects of Acute Transmural Pressure Elevation on Endothelium-Dependent Vasodilation in Isolated Rat Mesenteric Veins

Abstract

Background/Aims: The vascular regulatory function of the endothelium can be impaired by increases in transmural pressure (TMP). We tested the hypothesis that increasing TMP impairs the endothelial dilator function of rat mesenteric small veins (MSVs). Methods: In PGF2α-preconstricted MSVs, bradykinin (BK), sodium nitroprusside (SNP) and S-Nitroso-N-acetylpenicillamine (SNAP) concentration-response curves were generated at intermediate (6 mm Hg) and high (12 mm Hg) pressures. BK-induced vasodilation was examined in the absence and presence of nitric oxide synthase inhibitor [N^ω-nitro-<smlcap>L</smlcap>-arginine (<smlcap>L</smlcap>-NNA), 100 µ<smlcap>M</smlcap>], cyclooxygenase inhibitor (indomethacin, 1 µ<smlcap>M</smlcap>), and large (BK_Ca, paxilline, 500 n<smlcap>M</smlcap>) and small (SK_Ca, apamin, 300 n<smlcap>M</smlcap>) conductance Ca²⁺-activated K⁺ channel blockers. Results: BK, SNP and SNAP responses were not altered by TMP increases. BK-induced vasodilation was significantly reduced by <smlcap>L</smlcap>-NNA, indomethacin, apamin and paxilline at 6 mm Hg and <smlcap>L</smlcap>-NNA at 12 mm Hg, and was further reduced by coapplication of apamin and/or paxilline with <smlcap>L</smlcap>-NNA compared with responses obtained with either blocker. Endothelium removal completely abolished BK-induced vasodilation. Conclusion: Venous endothelial dilator function is not affected by TMP elevation. BK-induced vasodilation is completely dependent on the presence of functional endothelial cells and mediated in part by nitric oxide, BK_Ca and SK_Ca channels, while the participation of prostacyclin may be important at intermediate pressures.

A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension

“…SK expression in veins differs among organs and species. SK is expressed in the superior mesenteric vein in rats [9]. Expression of SK in portal veins has not been studied.…”