OXYGEN-DERIVED FREE-RADICALS CONTRIBUTE TO BARORECEPTOR DYSFUNCTION IN ATHEROSCLEROTIC RABBITS

The goal of the present study was to determine whether oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerosi s. Baroreceptor activity was measured from the carotid sinus nerve dur ing pressure ramps in isolated carotid sinuses of anesthetized rabbits . Rabbits fed a 0.5% to 1.0% cholestrol diet for 7.9+/-0.4 months (mea n+/-SE; range, 5.5 to 10) developed atherosclerotic lesions in the car otid sinuses. Maximum baroreceptor activity measured at 140 mm Hg and the slope of the pressure-activity curve were reduced in atherosclerot ic (n=15) compared with normal (n=13) rabbits (425+/-34 versus 721+/-3 0 spikes per second and 6.2+/-0.6 versus 10.8+/-0.8 spikes per second per mm Hg, respectively, P<.05). The level of activity was inversely r elated to plasma cholesterol concentration (r=.86, P<.001) and total c holesterol load (plasma concentrationXduration of diet, r=.92). Mean a rterial pressure was normal in both groups. Exposure of the carotid si nus to the free-radical scavengers superoxide dismutase (SOD) and cata lase significantly increased maximum baroreceptor activity by 25+/-4% in atherosclerotic rabbits (n=6) but caused only small and irreversibl e changes in activity in normal rabbits (n=8). Catalase alone but not SOD also increased baroreceptor activity in atherosclerotic rabbits (n =7). Exposure of the carotid sinus of normal rabbits to exogenous free radicals generated from the reaction between xanthine and xanthine ox idase inhibited baroreceptor activity in a dose-dependent and reversib le manner (n=8, P<.05). The inhibition of activity was attenuated by S OD and catalase but was not attenuated by the inhibitor of hydroxyl ra dical formation, deferoxamine. Neither restoration of baroreceptor act ivity in atherosclerotic rabbits by catalase nor inhibition of activit y by xanthine/xanthine oxidase could be explained by changes in the ca rotid pressure-diameter relation or prostacyclin formation. These resu lts indicate that oxidant stress inhibits baroreceptor activity and th at endogenous oxyradicals produced in atherosclerotic carotid sinuses sinuses contribute to baroreceptor dysfunction.