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Sphingosine‐1‐phosphate evokes vasoconstriction of rat afferent artreioles via activation of S1P1 and S1P2 receptors
Author(s) -
Guan Zhengrong,
Giddens Matthew I.,
Cook Anthony K.,
Inscho Edward W.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.665.24
Subject(s) - vasoconstriction , receptor , endocrinology , medicine , sphingosine 1 phosphate , agonist , sphingosine 1 phosphate receptor , chemistry , biology , anatomy , sphingosine
Sphingosine‐1‐phosphate (S1P) has emerged as a new regulator of vascular tone mainly via S1P1, 2, and 3 receptors. Our previous study using the in vitro blood‐perfused rat juxtamedullary nephron preparation showed that exogenous S1P potently vasoconstricted afferent but not efferent arterioles, suggesting a potential role of S1P in regulating microvascular resistance. The aim of this study is to determine which S1P receptors mediate vasoconstriction by S1P. Superfusion of FTY720, a non‐specific agonist for S1P1 and S1P3 receptors evoked concentration‐dependent vasoconstriction reducing arteriolar diameter to 87±2% (n=5) of control diameter (13.7±0.5 μm) at 10 −5 M. FTY720 was a significantly less potent vasoconstrictor than S1P (36±6% of control diameter at 10 −5 M, n=6). Application of a specific S1P2 receptor antagonist JTE013 (1 μM, n=5) did not significantly change baseline arteriolar diameter (15.8±0.6 vs. 16.2±0.6 μm), but shifted the S1P‐concentration curve to the right and abolished 10 −9 and 10 −8 M S1P‐induced vasoconstriction. In contrast, KCl (55 mM)‐induced vasoconstriction was not significantly changed (54±5%, n=5 vs. 40±6% without JTE013, n=14, p>0.05). Both S1P1 and S1P2 receptor proteins were detected in isolated preglomerular microvessels, whereas S1P3 was barely detected. These results suggest that S1P vasoconstricts afferent arterioles by activating S1P1 and S1P2 receptors. Studies supported by a Scientist Development Grant (10SDG3770010) from the American Heart Association.