Cardiovascular effects of adrenocorticotropin microinjections into the rostral ventrolateral medullary pressor area of the rat

The presence of adrenocorticotropic hormone (ACTH) immunoreactive cells and melanocortin (MC) receptors has been demonstrated in the medullary reticular formation in the general area encompassing rostral ventrolateral medullary pressor area (RVLM). The RVLM is an important cardiovascular regulatory area. Based on these reports, it was hypothesized that ACTH may play a role in the regulation of cardiovascular function. Experiments were carried out on artificially ventilated, adult, male, urethane‐anesthetized and unanesthetized mid‐collicular decerebrate rats. The RVLM was identified by microinjections of L‐glutamate (L‐Glu). Microinjections of ACTH (0.5, 1 and 2 mmol/L) into the RVLM elicited increases in mean arterial pressure and heart rate; tachycardic responses were relatively small and inconsistent. The effects of ACTH were blocked by prior microinjections of SHU9119 and agouti‐related protein (AGRP) into the RVLM. The specificity of these MC4 receptor antagonists was indicated by their lack of effect on L‐Glu‐induced responses. Prazosin (alpha‐1 adrenergic antagonist; 5 microgram/kg, i.v.) blocked the effects of ACTH and L‐Glu microinjected into the RVLM. It was concluded that: 1) ACTH exerts excitatory effects on RVLM neurons resulting in pressor and tachycardic responses, 2) these responses were mediated via MC4 receptors in the RVLM, and 3) the effects of ACTH were mediated via sympathetic activation of vascular alpha‐1 adrenergic receptors. This is the first report showing central cardiovascular actions of ACTH. Support: N.I.H. grants HL24347 and HL076248.