Role of oxygen-derived free radicals in acute angiotensin II--induced hypertensive vascular disease in the rat.

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Abstract
Severe experimental hypertension is associated with vascular hyperpermeability and cellular damage in small arteries and arterioles in rats. Oxygen-derived free radical production is also associated with increased vascular permeability and cellular injury in a variety of conditions, including ischemia-reperfusion and inflammation. To determine if free radicals play a role in the pathogenesis of hypertensive vascular disease, the free radical scavengers superoxide dismutase (SOD), catalase, SOD and catalase, and dimethyl sulfoxide (DMSO) were given to rats made acutely hypertensive with angiotensin II infusions. Untreated hypertensive and normotensive control animals were used for comparison. The effects of scavenger treatment were assessed by in vivo observations of intestinal small arteries by use of stereomicroscopy and videotape and light and transmission electron microscopy to identify and quantitate vascular lesions, and tracer particle injections to determine permeability changes. In vivo observations revealed that scavenger treatment did not alter vascular constriction patterns, vessel caliber, or blood pressures. Electron microscopy of arteries from untreated hypertensive rats showed more severe and more extensive endothelial and smooth muscle lesions, increased tracer particle penetration, and greater fibrin deposition than that found in scavenger-treated hypertensive groups. Quantitation of vascular lesions showed approximately equal reductions in smooth muscle necrosis (p less than 0.01) and fibrin deposition (p less than 0.05) in arteries from each of the scavenger-treated hypertensive groups. The results indicate that the free radical scavengers SOD, catalase, SOD-catalase, and DMSO inhibit (but do not prevent) vascular hyperpermeability and cellular damage during acute, angiotensin II--induced hypertension. These findings suggest that free radicals play a role in the pathogenesis of hypertensive vascular disease, probably by exacerbating the vascular changes initially triggered by an acute elevation in blood pressure.