In:
Clinical and Experimental Pharmacology and Physiology, Wiley, Vol. 46, No. 7 ( 2019-07), p. 643-651
Abstract:
Thromboxane A 2 ( TXA 2 ) has been implicated in the pathogenesis of vascular complications, but the underlying mechanism remains unclear. The contraction of renal arterial rings in mice was measured by a Multi Myograph System. The intracellular calcium concentration ([Ca 2+ ] i ) in vascular smooth muscle cells ( VSMC s) was obtained by using a fluo‐4/ AM dye and a confocal laser scanning microscopy. The results show that the U46619‐induced vasoconstriction of renal artery was completely blocked by a TXA 2 receptor antagonist GR 32191, significantly inhibited by a selective phospholipase C ( PI ‐ PLC ) inhibitor U73122 at 10 μmol/L and partially inhibited by a Phosphatidylcholine ‐ specific phospholipase C ( PC ‐ PLC ) inhibitor D609 at 50 μmol/L. Moreover, the U46619‐induced vasoconstriction was inhibited by a general protein kinase C ( PKC ) inhibitor chelerythrine at 10 μmol/L, and a selective PKC δ inhibitor rottlerin at 10 μmol/L. In addition, the PKC ‐induced vasoconstriction was partially inhibited by a Rho‐kinase inhibitor Y‐27632 at 10 μmol/L and was further completely inhibited together with a putative IP 3 receptor antagonist and store‐operated Ca 2+ ( SOC ) entry inhibitor 2‐ APB at 100 μmol/L. On the other hand, U46619‐induced vasoconstriction was partially inhibited by L‐type calcium channel (Cav1.2) inhibitor nifedipine at 1 μmol/L and 2‐ APB at 50 and 100 μmol/L. Last, U46619‐induced vasoconstriction was partially inhibited by a cell membrane Ca 2+ activated C1 − channel blocker 5‐Nitro‐2‐(3‐phenylpropylamino) benzoic acid ( NPPB ) at 50 and 100 μmol/L. Our results suggest that the U46619‐induced contraction of mouse intrarenal arteries is mediated by Cav1.2 and SOC channel, through the activation of thromboxane‐prostanoid receptors and its downstream signaling pathway.
Type of Medium:
Online Resource
ISSN:
0305-1870
,
1440-1681
DOI:
10.1111/cep.2019.46.issue-7
DOI:
10.1111/1440-1681.13087
Language:
English
Publisher:
Wiley
Publication Date:
2019
detail.hit.zdb_id:
2020033-X
SSG:
15,3
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