Chronic Activation of Dorsal Hindbrain Corticosteroid Receptors Augments the Arterial Pressure Response to Acute Stress

Abstract

Abstract-Augmented cardiovascular responses to acute stress can predict cardiovascular disease in humans. Chronic systemic increases in glucocorticoids produce enhanced cardiovascular responses to psychological stress; however, the site of action is unknown. Recent evidence indicates that glucocorticoids can act within the dorsal hindbrain to modulate cardiovascular function. Therefore, we tested the hypothesis that the endogenous glucocorticoid corticosterone can act in the dorsal hindbrain to enhance cardiovascular responses to restraint stress in conscious rats. Adrenal-intact animals with indwelling arterial catheters were treated for 4 or 6 days with 3-to 4-mg pellets of corticosterone or silastic (sham pellets) implanted on the dorsal hindbrain surface. Corticosterone pellets were also implanted either on the surface of the dura or subcutaneously to control for the systemic effects of corticosterone (systemic corticosterone). The integrated increase in arterial pressure during 1 hour of restraint stress was significantly (PϽ0.05) greater in dorsal hindbrain corticosterone (912Ϯ98 mm Hg per 60 minutes) relative to dorsal hindbrain sham (589Ϯ57 mm Hg per 60 minutes) or systemic corticosterone (592Ϯ122 mm Hg per 60 minutes) rats. The plasma glucose response after 10 minutes of stress was also significantly higher in dorsal hindbrain corticosterone-treated rats relative to both other groups. There were no significant between-group differences in the heart rate or corticosterone responses to stress. There were no differences in baseline values for any measured parameters. We conclude that corticosterone can act selectively in the dorsal hindbrain in rats with normal plasma corticosterone levels to augment the arterial pressure response to restraint stress. Key Words: glucocorticoids Ⅲ hypertension Ⅲ brain Ⅲ autonomic nervous system Ⅲ sympathetic nervous system Ⅲ nucleus of the solitary tract C hronic elevations in glucocorticoids increase cardiovascular disease risk. 1-3 Recent evidence suggests that glucocorticoid-mediated changes in neuroendocrine control of cardiovascular function could contribute to these adverse actions of glucocorticoids. For example, glucocorticoids reduce the sensitivity and increase the midpoint of the arterial baroreceptor reflex; similar changes in baroreflex function are positively associated with increased cardiovascular disease risk. 4 -7 Other studies have demonstrated that chronic systemic elevations in glucocorticoids increase the arterial pressure or norepinephrine response to acute stress. 8,9 Similar enhanced stress responses in humans have also been linked to increased cardiovascular disease risk. 10 However, the sites of action for stimulatory effects of glucocorticoids on cardiovascular function remain unknown.We demonstrated recently that, analogous to systemic increases in glucocorticoids, chronic treatment of the dorsal hindbrain (DHB) with the endogenous glucocorticoid corticosterone (Cort) attenuated the gain and increased the midpoint of baroreflex control of heart...

Prenatal high-salt diet in the Sprague-Dawley rat programs blood pressure and heart rate hyperresponsiveness to stress in adult female offspring

“…In adult rats, chronic increases in dorsal hindbrain corticosterone have been reported to produce an enhanced pressor response to restraint (35). However, in the present study, there was no difference in either basal or stressed corticosterone levels in NS vs. HS female offspring.…”

Chronic blockade of hindbrain glucocorticoid receptors reduces blood pressure responses to novel stress and attenuates adaptation to repeated stress

“…We previously demonstrated that chronic treatment of the DHB with exogenous corticosterone increased the arterial pressure and glucose responses to acute restraint stress in normotensive rats (56). The present study demonstrates that blockade of DHB GR with Mif attenuates the arterial pressure response to acute restraint stress in BHR, but has no affect on this response in WKY rats.…”

“…Other studies indicate that chronic, systemic elevations in glucocorticoids enhance cardiovascular and catecholamine responses to acute novel psychological stress (33,64). We demonstrated that chronic administration of the glucocorticoid corticosterone to the dorsal hindbrain (DHB) enhances the blood pressure and glucose responses to acute novel stress, without altering the systemic corticosterone or heart rate responses (56). Thus, exogenously administered glucocorticoids can act within the brain to modulate the cardiovascular response to psychological stress.…”

The effect of chronic peripheral nesfatin-1 application on blood pressure in normal and chronic restraint stressed rats: related with circulating level of blood pressure regulators

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