Hydrogen peroxide induces a greater contraction in mesenteric arteries of spontaneously hypertensive rats through thromboxane A(2) production.
1. Hydrogen peroxide (H(2)O(2)) 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(-3) M). 2. The contraction to H(2)O(2) in MA (E+ or E-) was greater in SHR than in WKY. Removal of endothelium potentiated the contraction to H(2)O(2) in WKY but not in SHR. Tachyphylaxis to H(2)O(2) was less prominent in SHR than in WKY. 3. The contraction of aorta to H(2)O(2) (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 H(2)O(2) (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(2)) inhibitor), indomethacin and diclofenac (cyclooxygenase (COX) inhibitors), and furegrelate (a TXA(2) synthase inhibitor). 5. Production of thromboxane B(2) induced by H(2)O(2) (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 H(2)O(2) 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 H(2)O(2) may be related to hypertension in SHR.
Gao
Y J
YJ
Department of Anaesthesia, McMaster University, Hamilton, Ontario, Canada.
Lee
R M
RM
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D046508:Culture Techniques; D004146:Dioxanes / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013618:Tachyphylaxis / Q000502:physiology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004146:Dioxanes; D004791:Enzyme Inhibitors; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; C057498:ICI 192605; D013929:Thromboxane B2; D013928:Thromboxane A2; C045749:SQ 29548; D006861:Hydrogen Peroxide