Effect of adrenomedullin infusion on basal and stimulated aldosterone secretion in conscious sheep with cervical adrenal autotransplants.
In vivo and in vitro studies have shown conflicting effects of adrenomedullin (ADM) on the secretion of steroid hormones from the adrenal gland. While some investigators report no effect of this peptide on the output of various hormones, others have reported both stimulatory and inhibitory roles for ADM. We have shown that basal aldosterone secretion rate (ASR), in conscious sheep with cervical adrenal autotransplants, did not change when ADM was infused directly into the adrenal arterial supply. While not affecting basal ASR, ADM did produce pronounced increases in adrenal blood flow (BF). This elevation of BF in association with ADM infusion was seen in all subsequent experiments. When aldosterone output was acutely stimulated by angiotensin II (AngII), potassium chloride (KCl) and adrenocorticotrophic hormone (ACTH), ADM was seen to drastically reduce the secretion of aldosterone with all agonists studied. After pre-exposure to ADM, all three agonists increased ASR but the magnitude of the responses were somewhat blunted. ADM did not have the same effect on cortisol secretion stimulated by ACTH, suggesting that the ability of this peptide to influence adrenal gland function is limited to the zona glomerulosa. In conditions of chronic elevation of aldosterone levels, such as in Na deficiency, ADM did not display the same inhibitory abilities seen in the acute stimulation experiments. Hence, ADM has been shown to have a direct, inhibitory role on the acute stimulation of aldosterone by AngII, KCl and ACTH while not affecting basal or chronic aldosterone secretion or cortisol secretion stimulated by ACTH.
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia. r.salemi@hfi.unimelb.edu.au
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Salemi
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McDougall
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Hardy
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Wintour
D000311:Adrenal Glands / Q000098:blood supply / Q000378:metabolism* / Q000637:transplantation; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D053607:Adrenomedullin; D000450:Aldosterone / Q000378:metabolism*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006854:Hydrocortisone / Q000378:metabolism; D007261:Infusions, Intra-Arterial; D010455:Peptides / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D013268:Stimulation, Chemical; D014182:Transplantation, Autologous
D010455:Peptides; D000804:Angiotensin II; D053607:Adrenomedullin; D000450:Aldosterone; D011189:Potassium Chloride; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone