Sphingosine‐1‐phosphate mediate vasoconstriction in femoral and mesenteric arteries of mice via S1P3 receptors

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We have previously shown that Sphingosine‐1‐phosphate (S1P) induces potent vasoconstriction in cerebral arteries by stimulating S1P(3) receptors, but little is known about the effect of S1P on femoral and mesenteric arteries. We therefore aimed to investigate the functional effect of S1P on femoral and mesenteric arteries of mice. Femoral and second or third branches of mesenteric arteries of C57BL/6 and S1P(3) receptor null male mice were isolated, mounted into a wire myograph. Constriction and relaxation responses were evaluated. S1P concentration‐dependently constricted both femoral and mesenteric arteries with intact endothelium in C57 mice but did not affect the vascular tone in arteries of S1P(3) null mice. Vasoconstriction to KCl and phenylephrine did not differ between C57 and S1P(3) null mice. After a preconstricton with submaximal concentration of phenylephrine, S1P and its vehicle induced a weak vasorelaxation in femoral and mesenteric arteries of both C57 and receptor null mice and these relaxations did not change in the presence of a nitric oxide synthase inhibitor, L‐NAME. Vasodilation to acethylcholine and sodium nitroprusside did not differ between C57 and S1P(3) null mice. Our findings suggest that S1P constricts femoral and mesenteric arteries of mice with intact endothelium through S1P(3) receptors and the vehicle of S1P causes a endothelium‐independent vasorelaxation.