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C‐reactive protein inhibits endothelium‐dependent prostacyclin synthase‐mediated dilation of coronary arterioles: role of peroxynitrite
Author(s) -
Hein Travis W.,
Qamirani Erion,
Shipley Robert D.,
Ren Yi,
Xu Xin,
Kuo Lih
Publication year - 2007
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.21.6.a1228-b
Subject(s) - peroxynitrite , chemistry , prostacyclin , vasodilation , endothelium , bradykinin , nitric oxide , medicine , endocrinology , apocynin , superoxide , pharmacology , reactive oxygen species , biochemistry , nadph oxidase , receptor , enzyme
We have recently shown that C‐reactive protein (CRP), a biomarker of cardiovascular disease, inhibits nitric oxide (NO)‐mediated vasodilation via NAD(P)H oxidase‐dependent superoxide (O 2 − ) production. Here, we examined whether CRP can influence the response to another endothelium‐derived vasodilator – prostacyclin (PGI 2 ). Porcine coronary arterioles were isolated and pressurized without flow for in vitro study. Endothelium‐dependent agonist arachidonic acid (AA) stimulated PGI 2 release and dilation. PGI 2 synthase (PGI 2 S) inhibitor trans ‐2‐phenyl cyclopropylamine blocked dilation to AA but not to endothelium‐dependent NO‐mediated agonist serotonin. Luminal administration of CRP (pathophysiologic level of 7 μg/ml, 60 min) attenuated dilations to serotonin and AA but not to exogenous PGI 2 . CRP also reduced basal NO level, caused tyrosine nitration of PGI 2 S, and inhibited PGI 2 release. Peroxynitrite scavenger urate prevented inhibitory actions of CRP on PGI 2 S and PGI 2 release/dilation but not on serotonin‐induced dilation. Moreover, NO synthase inhibitor L‐NAME or O 2 − scavenger TEMPOL prevented the detrimental effect of CRP on AA‐induced dilation. Our data show that CRP inhibits endothelium‐dependent PGI 2 S‐mediated dilation of coronary arterioles. This vascular dysfunction is a result of PGI 2 S nitration by peroxynitrite derived from basal NO and CRP‐induced O 2 − production. (HL‐71761 to LK)