Catecholamine release mediates pressor effects of adrermomedullin-(15-22) in the rat

被引:20
作者
Champion, HC [1 ]
Fry, RC [1 ]
Murphy, WA [1 ]
Coy, DH [1 ]
Kadowitz, PJ [1 ]
机构
[1] TULANE UNIV,SCH MED,DEPT PHARMACOL SL83,NEW ORLEANS,LA 70112
关键词
adrenomedullin; catecholamines; receptors; adrenergic; alpha; species specificity;
D O I
10.1161/01.HYP.28.6.1041
中图分类号
R6 [外科学];
学科分类号
1002 ; 100210 ;
摘要
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 N increased systemic aaerial 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. Presser responses to hADM-(15-22) were reduced significandy 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. Presser responses to DMPP were reduced by hexamethonium, whereas the nicotinic blocking agent had no effect on the presser 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 a-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.
引用
收藏
页码:1041 / 1046
页数:6
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