Glucocorticoids act in the dorsal hindbrain to increase arterial pressure.
Glucocorticoid receptors (GRs) are present at a high density in the nucleus of the solitary tract (NTS), an area of the dorsal hindbrain (DHB) that is critical for blood pressure regulation. However, whether these receptors play any role in the regulation of blood pressure is unknown. We tested the hypothesis that glucocorticoids act in the DHB to increase arterial pressure using two experimental strategies. In one approach, we implanted pellets of corticosterone (Cort) or sham pellets onto the DHB over the NTS. Compared with rats with sham pellets, rats with DHB Cort pellets had an increased (P < 0.05) mean arterial pressure (111 +/- 2 vs. 104 +/- 1 mmHg) and heart rate (355 +/- 9 vs. 326 +/- 5 beats/min) after 4 days. In the second approach, we implanted subcutaneous Cort pellets to increase the systemic Cort concentration and then subsequently implanted pellets of the GR antagonist mifepristone (Mif; previously RU-38486) or sham pellets onto the DHB. Two days of DHB Mif treatment reduced (P < 0.05) mean arterial pressure in those rats with elevated plasma Cort levels (118 +/- 2 vs. 108 +/- 1 mmHg for sham vs. Mif DHB pellets). Cort and Mif pellets placed on the dura had no effects on arterial pressure or heart rate, ruling out systemic cardiovascular effects of the steroids. DHB Cort treatment had no effects on plasma Cort concentration or adrenal weight, indicating that the contents of the DHB Cort pellet did not diffuse into the systemic circulation or into the forebrain areas that regulate plasma Cort concentration in concentrations sufficient to produce physiological effects. Immunohistochemistry for the occupied GRs demonstrated that the Cort and Mif from the DHB pellets were delivered to the DHB with minimal diffusion to the ventral hindbrain or forebrain. We conclude that glucocorticoids act in the DHB to increase arterial pressure.
D000311:Adrenal Glands / Q000033:anatomy & histology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm; D003345:Corticosterone / Q000493:pharmacokinetics / Q000494:pharmacology; D005938:Glucocorticoids / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D015735:Mifepristone / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism; D012249:Rhombencephalon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003345:Corticosterone