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

Abstract

Systemic corticosterone (Cort) modulates arterial baroreflex control of both heart rate and renal sympathetic nerve activity. Because baroreceptor afferents terminate in the dorsal hindbrain (DHB), an area with dense corticosteroid receptor expression, we tested the hypothesis that prolonged activation of DHB Cort receptors increases the midpoint and reduces the gain of arterial baroreflex control of heart rate in conscious rats. Small (3-4 mg) pellets of Cort (DHB Cort) or Silastic (DHB Sham) were placed on the surface of the DHB, or Cort was administered systemically by placing a Cort pellet on the surface of the dura (Dura Cort). Baroreflex control of heart rate was determined in conscious male Sprague Dawley rats on each of 4 days after initiation of treatment. Plots of arterial pressure vs. heart rate were analyzed using a four-parameter logistic function. After 3 days of treatment, the arterial pressure midpoint for baroreflex control of heart rate was increased in DHB Cort rats (123 +/- 2 mmHg) relative to both DHB Sham (108 +/- 3 mmHg) and Dura Cort rats (109 +/- 2 mmHg, P < 0.05). On day 4, baseline arterial pressure was greater in DHB Cort (112 +/- 2 mmHg) compared with DHB Sham (105 +/- 2 mmHg) and Dura Cort animals (106 +/- 2 mmHg, P < 0.05), and the arterial pressure midpoint was significantly greater than mean arterial pressure in the DHB Cort group only. Also on day 4, maximum baroreflex gain was reduced in DHB Cort (2.72 +/- 0.12 beats x min(-1) x mmHg(-1)) relative to DHB Sham and Dura Cort rats (3.51 +/- 0.28 and 3.37 +/- 0.27 beats x min(-1) x mmHg(-1), P < 0.05). We conclude that Cort acts in the DHB to increase the midpoint and reduce the gain of the heart rate baroreflex function.

Fig. 1

Mean arterial pressure (top) and heart rate (bottom) measured for 4 days in rats treated with dorsal hindbrain (DHB) or Dura pellets. P < 0.05 relative to DHB Sham (*) and relative to Dura Cort (+).

Fig. 2

Mean arterial pressure midpoint (top) and maximum baroreflex gain (bottom) on each day after DHB or Dura treatment. P < 0.05 relative to DHB Sham (*) and relative to Dura Cort (+).

Fig. 3

Average baroreflex function curves [calculated curves (top) and averaged raw data (bottom)] for rats on days 1 and 2 after treatment with DHB or Dura pellets. bpm, Beats/min.

Fig. 4

Average baroreflex function curves [calculated curves (top) and averaged raw data (bottom)] for rats on days 3 and 4 after treatment with DHB or Dura pellets.

Fig. 5

Comparison of baseline mean arterial pressure (MAP) and baroreceptor reflex (BRR) arterial pressure midpoint for each group on day 4. *P < 0.05 for a within-group difference between the 2 variables.