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Comparative Study
. 2001 Dec;134(8):1639-46.
doi: 10.1038/sj.bjp.0704420.

Hydrogen peroxide induces a greater contraction in mesenteric arteries of spontaneously hypertensive rats through thromboxane A(2) production

Y J Gao  1 , R M Lee
Affiliations
Comparative Study

Hydrogen peroxide induces a greater contraction in mesenteric arteries of spontaneously hypertensive rats through thromboxane A(2) production

Y J Gao et al. Br J Pharmacol. 2001 Dec.

Abstract

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.

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Figures

Figure 1
Figure 1
(A) Typical tracings showing the contractile effects of hydrogen peroxide (H2O2, 10−5 M, 10−4 M, and 10−3 M) in WKY and SHR mesenteric arteries with intact (E+) or denuded (E−) endothelium. (B) Concentration-response relation of H2O2. Results (mean±s.e.mean) were from 4 – 6 rats and expressed as the percentage of the contraction elicited by 80 mM KCl. *P<0.05, compared with respective E+ arteries; #P<0.05, ##P<0.01 between SHR and respective WKY arteries with or without endothelium.
Figure 2
Figure 2
(A) Contractile effects of H2O2 (5×10−4 M) on the mesenteric artery with (E+) or without (E−) endothelium from SHR and WKY. *P<0.05 compared with E+ arteries; #P<0.05, ##P<0.01, compared with WKY arteries. (B) Effects of dimethylsulphoxide (DMSO, 5 mM), catalase (1000 u/ml), and superoxide dismutase (SOD, 150 u/ml) on the contraction induced by H2O2 (5×10−4 M) in the E+ mesenteric artery of 4 – 6 rats each from WKY and SHR. **P<0.01 compared with their respective control.
Figure 3
Figure 3
(A) Comparison of the contractile effects of H2O2 (5×10−4 M) on the mesenteric artery (MA) and the aorta, with (E+) or without (E−) endothelium, from SHR and WKY. *P<0.05, **P<0.01 compared with aorta; (B) Contraction to H2O2 (5×10−4 M) in E+ and E− aorta from SHR and WKY. **P<0.01, compared with WKY aorta, #P<0.05 compared with E+ rings. Results (mean±s.e.mean) were from 6 – 11 rats and expressed as the percentage of the contraction elicited by 80 mM KCl.
Figure 4
Figure 4
Tachyphylaxis of the contraction by H2O2 (5×10−4 M) in endothelium-denuded mesenteric artery from WKY and SHR. Results (mean±s.e.mean) were from four each of SHR or WKY and expressed as the percentage of the contraction elicited by 80 mM KCl. **P<0.01 compared with respective WKY arteries.
Figure 5
Figure 5
(A) Inhibitory effects of SQ 29548 and ICI 192605 on H2O2 (5×10−4 M) induced contraction in the endothelium-denuded (E−) mesenteric artery from WKY and SHR. Results (mean±s.e.mean) were from four each of SHR or WKY and expressed as the percentage of the contraction of the control arteries. (B) Contraction by U46619 in the E− mesenteric artery from WKY and SHR. Results (mean±s.e.mean) were from four each of SHR or WKY and expressed as the percentage of the contraction elicited by 80 mM KCl.
Figure 6
Figure 6
Inhibitory effects of quinacirne, indomethacin, diclofenac, and furegrelate on the contraction induced by H2O2 (5×10−4 M) in E− mesenteric artery from WKY and SHR. Results (mean±s.e.mean) were from four each of SHR or WKY and expressed as the percentage of the contraction in the control arteries.
Figure 7
Figure 7
Thromboxane B2 (TXB2) production (pg/mg wet tissue), stimulated by H2O2 (5×10−4 M), and the effects of enzyme inhibitors (quinacirne, indomethacin, diclofenac, and furegrelate) and of thromboxane A2 and/or prostaglandin H2 receptor antagonists (SQ 29548 and ICI 192605) in E− mesenteric artery from WKY and SHR. Results (mean±s.e.mean) were from 4 – 6 rats each from SHR and WKY. *P<0.05, **P<0.01 compared with respective pre-stimulation level; ##P<0.01, compared with H2O2; $P<0.05 compared with respective WKY.
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