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(Hypertension. 1996;28:1041-1046.)
© 1996 American Heart Association, Inc.

Articles

Catecholamine Release Mediates Pressor Effects of Adrenomedullin-(15-22) in the Rat

Hunter C. Champion; Rebecca C. Fry; William A. Murphy; David H. Coy; Philip J. Kadowitz

the Department of Pharmacology, Tulane University School of Medicine, New Orleans, La.

Correspondence to Philip J. Kadowitz, PhD, Department of Pharmacology SL83, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112.

Human adrenomedullin, a novel hypotensive peptide, contains a six-member ring structure similar to that found in calcitonin gene–related peptide and pancreatic amylin. Unlike the full-sequence peptide, human adrenomedullin-(15-22) [hADM-(15-22)], which contains the ring structure, increases systemic arterial pressure in the rat but not the cat. We undertook the present study to investigate the mechanism by which hADM-(15-22) increases systemic arterial pressure in the rat. Injection of hADM-(15-22) in doses of 10 to 300 nmol/kg IV increased systemic arterial pressure in a dose-dependent manner and was threefold less potent than norepinephrine when doses were compared on a nanomole basis. However, the ring structures of human calcitonin gene–related peptide and human amylin, human calcitonin gene–related peptide-(1-8) and human amylin-(1-8), respectively, had no significant effect on systemic arterial pressure in the rat. Pressor responses to hADM-(15-22) were reduced significantly after administration of phentolamine or reserpine. Responses to hADM-(15-22) were not altered by the angiotensin type 1 blocking agent DuP 753 or the endothelin-A/endothelin-B receptor blocking agent bosentan, and responses to hADM-(15-22) and the nicotinic agonist 1,1-dimethyl-4-phenylpiperazinium (DMPP) were reduced after bilateral adrenalectomy. Pressor responses to DMPP were reduced by hexamethonium, whereas the nicotinic blocking agent had no effect on the pressor response to hADM-(15-22). These data suggest that increases in systemic arterial pressure in response to hADM-(15-22) in the rat are mediated by the activation of -adrenergic receptors by catecholamines released from the adrenal medulla. The present data suggest that hADM-(15-22) releases catecholamines from the adrenal medulla by a noncholinergic mechanism.

Key Words: adrenomedullin • catecholamines • receptors, adrenergic, alpha • species specificity

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