Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 134, Issue 8, Pages 1639-1646Publisher
WILEY
DOI: 10.1038/sj.bjp.0704420
Keywords
hydrogen peroxide; hypertension; mesenteric artery; reactive oxygen species; spontaneously hypertensive rats; thromboxane A(2); Wistar-Kyoto rats
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1 Hydrogen peroxide (H2O2) caused a transient contraction in endothelium-intact (E+) and -denuded (E-) mesenteric arteries (MA) from 8-10-month-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) in a concentration-dependent manner (10-(5) M to 10(-1) M). 2 The contraction to H2O2 in MA (E + or E -) was greater in SHR than in WKY. Removal of endothelium potentiated the contraction to H2O2 in WKY but not in SHR. Tachyphylaxis to H2O2 was less prominent in SHR than in WKY. 3 The contraction of aorta to H2O2 (5 x 10(-4) M), expressed as a percentage of 80 mM KCl-induced contraction, was approximately half of that found in the MA. A greater contraction was found in E+ but not E- SHR aortic rings. 4 The contraction of MA to H2O2 (5 x 10(-4) M) was greatly inhibited by SQ 29548 and ICI 192605 (thromboxane A(2) (TXA(2))/prostaglandin H-2 receptor antagonists), quinacrine (a phospholipase A(2) (PLA,) inhibitor), indomethacin and diclofenac (cyclooxygenase (COX) inhibitors), and furegrelate (a TXA(2) synthase inhibitor). 5 Production of thromboxane B-2 induced by H2O2 (5 x 10(-4) M) was greater in SHR MA than in WKY, and was inhibited by quinacrine, indomethacin and diclofenac, and furegrelate, but not by SQ 29584 and ICI 192605. 6 These results suggested (1) that SHR MA exhibits a higher contraction involving an increased smooth muscle reactivity and less tachyphylaxis to H2O2 than WKY; (2) that a greater production of TXA(2) through activation of PLA(2)-COX-TXA(2) synthase pathway appeared to be responsible for the enhanced contraction in SHR MA. The enhanced vascular response to H2O2 may be related to hypertension in SHR.
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