Oxygen-Derived Free Radicals Contribute to Baroreceptor Dysfunction in Atherosclerotic Rabbits

Abstract

The goal of the present study was to determine whether oxygen-derived free radicals contribute to baroreceptor dysfunction in atherosclerosis. Baroreceptor activity was measured from the carotid sinus nerve during pressure ramps in isolated carotid sinuses of anesthetized rabbits. Rabbits fed a 0.5% to 1.0% cholesterol diet for 7.9 +/- 0.4 months (mean +/- SE; range, 5.5 to 10) developed atherosclerotic lesions in the carotid sinuses. Maximum baroreceptor activity measured at 140 mm Hg and the slope of the pressure-activity curve were reduced in atherosclerotic (n = 15) compared with normal (n = 13) rabbits (425 +/- 34 versus 721 +/- 30 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 related to plasma cholesterol concentration (r = .86, P < .001) and total cholesterol load (plasma concentration x duration of diet, r = .92). Mean arterial pressure was normal in both groups. Exposure of the carotid sinus to the free-radical scavengers superoxide dismutase (SOD) and catalase significantly increased maximum baroreceptor activity by 25 +/- 4% in atherosclerotic rabbits (n = 6) but caused only small and irreversible 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 oxidase inhibited baroreceptor activity in a dose-dependent and reversible manner (n = 8, P < .05). The inhibition of activity was attenuated by SOD and catalase but was not attenuated by the inhibitor of hydroxyl radical formation, deferoxamine. Neither restoration of baroreceptor activity in atherosclerotic rabbits by catalase nor inhibition of activity by xanthine/xanthine oxidase could be explained by changes in the carotid pressure-diameter relation or prostacyclin formation. These results indicate that oxidant stress inhibits baroreceptor activity and that endogenous oxyradicals produced in atherosclerotic carotid sinuses contribute to baroreceptor dysfunction.

Differential modulation of baroreflex control of heart rate by neuron- vs. glia-derived angiotensin II

“…For example, acute increases in BP lead to resetting of the BP-afferent baroreceptor activity curve (1). In contrast, aging and atherosclerosis can decrease baroreceptor gain in the absence of any baroreceptor resetting (2,20,22). Decreased baroreceptor gain translates to an impaired ability to buffer fluctuations in BP and is thought to be important pathologically.…”

Increased prevalence of Chlamydophila pneumoniae but not Epstein–Barr antibodies in essential hypertensives

“…It has been demonstrated that atherosclerotic alteration in the architecture of the vessel wall, where baroreceptive endings terminate, is considered the predominant mechanism responsible for the degreased baroreflex sensitivity, leading eventually to hypertension. [41][42][43][44] Accepting the theory that C. pneumoniae contributes to the pathogenesis of atherosclerosis, the settlement of this microorganism in these vessel areas, by inducing a chronic immune response orchestrated by cytokines, activation of monocytes and changes in lipid profile, contributes to structural injury of intima and media. Consequently, the findings of the present study provide suggestive evidence that C. pneumoniae contributes as a risk factorFcombined with otherFto the genesis of hypertension.…”

Oxidative stress and baroreflex sensitivity in healthy subjects and patients with mild-to-moderate hypertension

“…10 Oxidative stress alters BRS in animal models: exposure of atherosclerotic sinuses of rabbits to free radical scavengers (superoxide dismutase and catalase) increased baroreceptor activity; conversely, free radical generation by the chemical reaction of xanthine and xanthine oxidase suppressed baroreceptor activity in a normal carotid sinus. 11 Conversely, antioxidant treatment with alpha-lipoic acid 12 or vitamin E 13 for four months improved autonomic neuropathy and HR variability in NIDDM patients. However, there is no clear evidence that BRS is correlated to oxidative stress in healthy subjects and hypertensive patients.…”