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Am J Physiol Heart Circ Physiol 275: H1585-H1591, 1998;
0363-6135/98 $5.00
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Vol. 275, Issue 5, H1585-H1591, November 1998

Peroxynitrite is a contractile agonist of cerebral artery smooth muscle cells

Stephen J. Elliott, David J. Lacey, William M. Chilian, and Anna K. Brzezinska

Department of Pediatrics and Cardiovascular Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226

On reperfusion of ischemic tissue, a prolonged phase of vasoconstriction occurs, the mechanism of which is poorly understood. However, it is known that peroxynitrite (ONOO-) is formed during reperfusion. In this study the contractile properties of ONOO- were investigated in Wistar rat middle cerebral arteries. The effects of ONOO- on vessel diameter were dose dependent. Low-dose ONOO- (10 µM) caused vessels to constrict by 15%. At an intermediate concentration of 25 µM, the effect of ONOO- was variable, whereas at the highest concentration (100 µM), vessels underwent persistent dilation and became insensitive to the endogenous vasoconstrictor 5-hydroxytryptamine. At the single cell level, ONOO- caused cerebral artery smooth muscle cells to contract. Reduced, but not oxidized, glutathione completely inhibited the contractile action of ONOO- on single cells. Vehicle and decomposed ONOO- each had minimal effect on cell length. These data show that ONOO- is a contractile agonist of middle cerebral arteries, at the single cell and whole vessel levels, suggesting that formation of ONOO- may contribute mechanistically to ischemic brain injury during stroke. Moreover, relatively high concentrations of ONOO- result in vascular paralysis.

vascular smooth muscle cell; free radical; oxidant; glutathione; ischemia-reperfusion


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