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 (MC4 and to a lesser extent MC3) has been demonstrated in the medullary reticular formation in the general area where rostral ventrolateral medullary pressor area (RVLM) is located. The importance of RVLM in the regulation of cardiovascular function is well established. Based on these reports, it was hypothesized that ACTH may play a role in the regulation of cardiovascular function. To test this hypothesis, experiments were carried out on artificially ventilated, adult male, urethane-anesthetized and unanesthetized mid-collicular decerebrate rats. The RVLM was identified by microinjections (100 nl) of L-glutamate (L-Glu). Microinjections (100 nl) of ACTH (0.5, 1 and 2 mmol/l) into the RVLM elicited increases in MAP and HR; tachycardic responses were relatively inconsistent. The effects of ACTH were blocked by SHU9119 and agouti-related protein (AGRP). SHU9119 (a synthetic compound) and AGRP (an endogenous peptide) are antagonists for MC4, and to a lesser extent MC3, receptors. The specificity of these antagonists for MC receptors was indicated by their lack of effect on l-Glu responses. Microinjection of ACTH into the RVLM increased the efferent discharge in the greater splanchnic nerve. 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 and to a lesser extent MC3 receptors in the RVLM, and (3) the pressor effects of ACTH were mediated via sympathetic activation. This is the first report showing central cardiovascular actions of ACTH.
Kawabe
Tetsuya
T
Department of Neurological Surgery, MSB H-586, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, 07103, USA.
Chitravanshi
Vineet C
VC
Kawabe
Kazumi
K
Sapru
Hreday N
HN
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D054369:Agouti-Related Protein; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D003655:Decerebrate State; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006728:Hormones / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008845:Microinjections / Q000379:methods; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D054369:Agouti-Related Protein; D006727:Hormone Antagonists; D006728:Hormones; D010446:Peptide Fragments; C430443:agouti-related protein (86-132), human; C103272:SHU 9119; D018698:Glutamic Acid; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones