Actions of glucocorticoids on the arterial baroreceptor reflex

Glucocorticoids are essential for normal cardiovascular function. However, elevated glucocorticoids produce hypertension, and evidence is accumulating that glucocorticoids contribute to the pathogenesis of essential hypertension. Nonetheless, the effects of glucocorticoids on neural control of the circulation are poorly understood. Therefore, experiments were performed in inactin anesthetized Male Sprague-Dawley rats to determine the effects of chronic corticosterone (cort) treatment on reflex control of arterial pressure (AP) and renal sympathetic nerve activity (RSNA). In the first series of experiments, the baroreceptor reflex was activated in control (con; n=3) and cort (n=3) rats by microinjection of glutamate (100 pmol in 100 nl) into the nucleus of the solitary tract. Glutamate produced a larger (P<0.05) reduction in AP in con vs cort rats (-25±3 vs 16±2 mmHg). In a second series of experiments, reflex control of RSNA was determined, using intravenous infusions of phenylephrine and nitroprusside to change AP at the rate of 1-2 mmHg/sec, before and 2 and 3 hrs after administration of the glucocorticoid type II receptor antagonist Mifepristone (Mif; 30 mg/Kg s.c.). Reflex curves were analyzed using a 4 parameter logistic function. Baseline MAP (126±2 vs. 114±3 mmHg) and HR(417±6 vs. 379±5 bpm) were greater (P<0.05) in cort (n=10) vs con (n=7) rats. RSNA, as a percentage of maximum, was 70±2 and 74±3% in con and cort rats, respectively. The pressure at midrange of the RSNA baroreflex curve in cort rats was 137±2 mmHg before Mif, and was shifted to the left (126±2 and 123±2 mmHg; P<0.05) 2 and 3 hrs following Mif. There was also a tendency for gain to increase in cort rats after Mif. In con rats pressure at midrange was 125±4 mmHg before Mif, and was not decreased significantly until 3 hrs after Mif. These results suggest that chronic elevations in cort modulates baroreflex regulation.