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Mechanisms involved in the regional haemodynamic effects of intermedin (adrenomedullin 2) compared with adrenomedullin in conscious rats
Author(s) -
Jolly L,
March JE,
Kemp PA,
Bennett T,
Gardiner SM
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00306.x
Subject(s) - adrenomedullin , vasodilation , hemodynamics , medicine , in vivo , endocrinology , mesenteric arteries , pharmacology , receptor , biology , artery , microbiology and biotechnology
Background and purpose: Intermedin (IMD) is a newly identified member of the calcitonin family of peptides that shares structural and functional homology with adrenomedullin (AM). In vivo cardiovascular effects of AM have been described, but relatively little is known of the in vivo actions of IMD. The purpose of this study was to compare the regional haemodynamic effects of IMD with those of AM in conscious rats, and investigate possible underlying mechanisms. Experimental approach: Measurements of blood pressure, heart rate and renal, mesenteric and hindquarters haemodynamics were made in conscious, chronically‐instrumented rats. Key results: IMD caused tachycardia and vasodilatation in all three vascular beds, associated with modest hypotension. At an equimolar dose (1 nmol·kg −1 ), most of the cardiovascular effects of IMD were greater than those of AM. The AM receptor antagonist, AM 22–52 , was equally effective in attenuating the renal and mesenteric vasodilator effects of IMD (1 nmol·kg −1 ) and AM (3 nmol·kg −1 ), but inhibition of NO synthase was more effective at reducing the vasodilator effects of IMD than AM. Vascular K ATP channel blockade with U‐37883A did not inhibit the vasodilator effects of either peptide. Conclusions and implications: In vivo , the regional haemodynamic profile of IMD resembles that of AM, and some of the vasodilator effects of IMD are mediated by AM receptors and NO, but not by K ATP channels. The cardiovascular effects of AM have been implicated in various pathological conditions, but whether or not endogenous IMD fulfils a similar role remains to be determined.