Augmented sphingosylphosphorylcholine-induced Ca2+-sensitization of mesenteric artery contraction in spontaneously hypertensive rat

Naunyn-Schmiedeberg's Archives of Pharmacology
Sung-Kyung RyuYoung-Ho Lee

Abstract

Sphingosylphosphorylcholine (SPC) is a vasoconstricting lysosphingolipid, and the RhoA/Rho-kinase pathway plays an important role in SPC-induced contraction. Since RhoA/Rho-kinase-mediated signaling is involved in the generation and/or maintenance of hypertension, we compared the effect of SPC on the contractility of endothelium-denuded small mesenteric arteries in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Fura-2 Ca2+ signals, contractile responses, and phosphorylation of 20-kDa myosin light chains (MLC20) were measured. Ten microM SPC induced a gradual and sustained vasoconstriction, which was greater in arteries of the SHR (82.5 +/- 4.3%, n=9) than in those of the WKY (26.7 +/- 4.5%, n=10). In Ca2+-free media, SPC gradually increased vascular tone in the SHR, but caused little vasoconstriction in the WKY. In the SHR and WKY, SPC evoked a greater vasoconstriction than did high K+ depolarization at a given Ca2+ ratio, and the Ca2+ ratio-tension curve induced by SPC was significantly shifted to the left compared with that induced by high K+ depolarization. However, the magnitude of shift to the left was greater in the SHR than in the WKY. The Rho-kinase inhibitor Y-27632 significantly inhibited SPC-induc...Continue Reading

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Citations

Mar 30, 2006·Naunyn-Schmiedeberg's Archives of Pharmacology·Denise G Hemmings
Oct 14, 2011·Naunyn-Schmiedeberg's Archives of Pharmacology·Hye Young KimIn Kyeom Kim
Apr 22, 2010·Biochemical and Biophysical Research Communications·Hae-Ahm LeeIn Kyeom Kim
Mar 30, 2007·Acta Paediatrica. Supplement·Martin C MichelStephan L M Peters
Jan 20, 2015·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Young-Hwan KimSeungsoo Chung
Mar 12, 2010·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Enyue YangIn Kyeom Kim

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