Responses of the rat pituitary-adrenal axis to hypotensive infusions of corticotropin-releasing factor, vasoactive intestinal peptide and other depressor agents


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Responses of the rat pituitary-adrenal axis to hypotensive infusions of corticotropin-releasing factor, vasoactive intestinal peptide and other depressor agents
Regulatory Peptides
Pralong  F. P., Corder  R., Gaillard  R. C.
0167-0115 (Print)
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Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Feb 1
We have assessed in male rats the response of the hypothalamo-pituitary-adrenal axis to hypotension induced by 30 min i.v. infusions of corticotropin-releasing factor (CRF; 0.1, 0.2 and 0.5 nmol/kg/min), calcitonin gene-related peptide (CGRP; 0.25 nmol/kg/min), vasoactive intestinal peptide (VIP; 0.25 nmol/kg/min) and nitroprusside (NP; 150 micrograms/kg/min). Infusions of CRF produced dose-dependent decreases in mean arterial blood pressure of 10, 35 and 43 mmHg at 30 min, and the other treatment had depressor effects comparable with the higher CRF doses (between -35 and -44 mmHg). Plasma ACTH levels were increased from 383% to 595% by CGRP, NP and the three different CRF infusions (P less than 0.001 vs. controls), whereas they were raised more than 10-fold by VIP administration (P less than 0.001 vs. other treatments), a level 60% higher than the maximum achieved with CRF. Corticosterone levels were increased by 112% to 146% following infusion of the three different CRF doses, CGRP and NP (P less than 0.001 vs. controls), and by 240% after VIP (P less than 0.001 vs. other treatments). Plasma aldosterone values were increased by 112% to 140% after infusion of NP and the two higher CRF doses (P less than 0.01 vs. controls), and by 223% following VIP (P less than 0.05 vs. CRF 0.2 and NP). CGRP infusion, although resulting in similar haemodynamic changes, did not alter circulating aldosterone. The levels measured after CGRP were identical to those observed after the infusion of atrial natriuretic peptide (ANP; 1 nmol/kg/min), a known inhibitor of aldosterone secretion. These results demonstrate that the combination of hypotension and direct pituitary stimulation by CRF does not increase circulating ACTH levels above those obtained with hypotension alone (NP and CGRP), whereas VIP, which has only minimal direct effects on corticotroph function, markedly enhanced the ACTH response, suggesting that it may modulate ACTH release by an indirect mechanism. Evaluation of aldosterone levels after the different infusions indicates that CGRP prevented the rise normally associated with acute hypotension, thus confirming recent observations in other species that stimulated aldosterone secretion can be inhibited by CGRP.
Adrenocorticotropic Hormone/blood Aldosterone/*blood Animals Blood Pressure/drug effects Calcitonin Gene-Related Peptide/*pharmacology Corticosterone/*blood Corticotropin-Releasing Hormone/*pharmacology Heart Rate/drug effects Hypotension/*metabolism Hypothalamo-Hypophyseal System/drug effects/*metabolism Male Pituitary-Adrenal System/drug effects/*metabolism Rats Rats, Inbred Strains Vasoactive Intestinal Peptide/pharmacology
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25/01/2008 17:26
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20/08/2019 16:20
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