Glucocorticoids modulate baroreflex control of renal sympathetic nerve activity

Abstract

Experiments were performed to determine the effects of glucocorticoids on arterial baroreceptor reflex control of renal sympathetic nerve activity (RSNA). Intravenous infusions of phenylephrine and nitroprusside were used to produce graded changes in arterial pressure (AP) in Inactin-anesthetized male Sprague-Dawley rats. Baroreflex control of RSNA was determined during a baseline period and 2 and 3 h after administration of the glucocorticoid type II receptor antagonist Mifepristone (30 mg/kg sc) or vehicle (oil). Corticosterone (cort) treatment (100 mg cort pellet sc for 2-3 wk) increased baseline AP from 115 +/- 2 to 128 +/- 1 mmHg. Cort treatment also decreased the gain coefficient and increased the midpoint of the baroreflex curve. Treatment of cort rats with Mifepristone decreased AP within 2 h and increased the gain coefficient and decreased the midpoint of the baroreflex function curve back toward values measured in control rats. Mifepristone altered the baroreflex function curve even when AP was maintained at baseline levels. Therefore, these data demonstrate for the first time that glucocorticoids can modulate baroreflex control of RSNA by a mechanism that is, in part, independent of changes in AP.

Glucocorticoids act in the dorsal hindbrain to modulate baroreflex control of heart rate

“…We have also reported that systemic administration of the GR antagonist Mifepristone reverses effects of systemic Cort to modulate baroreflex control of heart rate and renal sympathetic nerve activity (37,40). However, we have not determined if the effects of Cort in the DHB on baroreflex function are mediated by MRs, GRs, or by a combined action of both receptors.…”

“…Previous studies from this and other laboratories have demonstrated that systemic glucocorticoid administration can increase the arterial pressure midpoint and decrease the gain of baroreflex control of heart rate and renal sympathetic nerve activity (37,40,(42)(43)(44). However, the sites of action of Cort to modulate baroreflex function have not been determined.…”

“…In the present study, baseline heart rate was elevated on day 3 in DHB Cort rats, but only relative to DHB Sham rats, whereas in the previous study we reported an increase in DHB Cort rats relative to both Dura Cort and DHB Sham rats on day 4. We have previously observed a variable effect of Cort on baseline heart rate (37,40).…”

“…Many of these risk factors are also associated with dysregulation of autonomic function (2, 14, 36). However, the mechanisms by which glucocorticoids modulate arterial pressure regulation, particularly with respect to the effects of glucocorticoids on central pathways controlling autonomic function, remain poorly understood.Studies in animals indicate that systemic elevations in glucocorticoids can modulate the function of the arterial baroreceptor reflex (12,37,40,(42)(43)(44). The arterial baroreceptor reflex is an autonomic reflex that is important for the shortterm, and possibly long-term, regulation of arterial pressure (3,29,32,50).…”

“…The arterial baroreceptor reflex is an autonomic reflex that is important for the shortterm, and possibly long-term, regulation of arterial pressure (3,29,32,50). Studies from our laboratory have demonstrated that systemic administration of corticosterone (Cort) modulates baroreflex control of both renal sympathetic nerve activity and heart rate to increase the arterial pressure midpoint and decreases the reflex gain independent of changes in arterial pressure in rats (37,40). Studies from Segar et al (42)(43)(44) demonstrate that glucocorticoids increase the midpoint and reduce the gain of the arterial baroreflex during the perinatal period.…”