Mechanisms involved in the regional haemodynamic effects of intermedin (adrenomedullin 2) compared with adrenomedullin in conscious rats.
OBJECTIVE
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.


METHODS
Measurements of blood pressure, heart rate and renal, mesenteric and hindquarters haemodynamics were made in conscious, chronically-instrumented rats.


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
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.
Jolly
L
L
Centre for Integrated Systems Biology & Medicine, School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
March
J E
JE
Kemp
P A
PA
Bennett
T
T
Gardiner
S M
SM
D053607:Adrenomedullin / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects; D013610:Tachycardia / Q000139:chemically induced; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
C499411:Adm2 protein, rat; D009479:Neuropeptides; D014665:Vasodilator Agents; D053607:Adrenomedullin
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