Effects of systemic and dorsal hindbrain glucocorticoids on arterial baroreceptor reflex control of heart rate

Elevated glucocorticoids can contribute to the development of hypertension and cardiovascular disease, yet the underlying mechanims mediating these effects remain unclear. The arterial baroreflex is a primary regulator of blood pressure that may contribute to effects of glucocorticoids on cardiovascular function. Therefore, experiments were performed to investigate the effects of elevated glucocorticoids on baroreflex function in conscious rats. First, arterial baroreceptor reflex control of heart rate was determined in rats treated for 4-6 days with systemic Cort, to determine the effect of systemic Cort elevations on baroreflex function. Cort treatment significantly increased the mean arterial blood pressure midpoint and decreased the slope of the heart rate baroreflex function curve. These baroreflex parameters returned to control values three hours after of treatment with Mifepristone (Mif), a glucocorticoid type II (GR) receptor antagonist. Mif had no effect on baroreflex function in control rats. Next, the contribution of the DHB, an important central nervous system site that regulates baroreflex function, to glucocorticoid mediated effects on arterial blood pressure was determined by implantation of pellets of Cort, Mif or silastic (control) onto the DHB. DHB Cort treatment increased mean arterial blood pressure and heart rate within 4 days of treatment in rats with normal plasma Cort levels, while DHB Mif treatment reduced mean arterial blood pressure in rats with elevated systemic Cort levels. Finally, the effect of DHB Cort on baroreflex control of heart rate was determined in rats treated with DHB Cort or DHB sham pellets. DHB Cort treatment increased the arterial blood pressure midpoint and decreased the gain of heart rate baroreflex function by day 3 and 4 of treatment, respectively. Immunohistochemistry demonstrated that the Cort and Mif from the DHB pellets were delivered to the DHB with minimal diffusion to the ventral hindbrain or other forebrain structures. We conclude that glucocorticoids modulate arterial blood pressure and baroreflex control of heart rate, in part by acting in the DHB. These studies provide new information regarding the effects of glucocorticoids acting in the central nervous system to control blood pressure.