Effects of adrenomedullin on human myocyte contractile function and beta-adrenergic response.
BACKGROUND
Adrenomedullin has been demonstrated to cause systemic vasodilation, and increased plasma adrenomedullin levels have been observed in cardiovascular disease states such as heart failure. While adrenomedullin receptors have been localized to the myocardium, the effects of adrenomedullin on human myocyte contractility remained unknown.


RESULTS
Left ventricular myocytes were isolated from myocardial biopsies of patients (n = 16) undergoing elective coronary artery bypass surgery with normal left ventricular ejection fractions (51 +/- 1%). A total of 233 left ventricular myocytes were studied by videomicroscopy. Myocyte shortening velocity (microm/s) was measured at baseline and following the addition of either 3 nM, 30 nM, or 60 nM of adrenomedullin. The change in myocyte shortening velocity with increasing concentrations of adrenomedullin was computed. At all concentrations, adrenomedullin reduced myocyte shortening velocity from baseline values (P < 0.05). Next, the potential interaction of adrenomedullin with the beta-adrenergic receptor system was examined using 25 nM isoproterenol. The beta-adrenergic receptor-mediated increase in the myocyte shortening velocity was blunted with adrenomedullin (29 +/- 7 vs 63 +/- 13 microm/s, P < 0.05).


CONCLUSIONS
These unique findings demonstrate that adrenomedullin reduced contractility in isolated human left ventricular myocytes and exhibited a negative interaction with the beta-adrenergic receptor system. Past studies have shown that adrenomedullin induces nitric oxide synthesis and that nitric oxide can uncouple myocyte metabolism. Thus, while adrenomedullin causes systemic vasodilation, this peptide can also exert a negative contractile effect in human left ventricular myocytes.
Mukherjee
Rupak
R
Department of Surgery, Medical University of South Carolina, Charleston, SC 29425, USA.
Multani
M Marlina
MM
Sample
Jeffrey A
JA
Dowdy
Kathryn B
KB
Zellner
James L
JL
Hoover
Donald B
DB
Spinale
Francis G
FG
D053607:Adrenomedullin; D000368:Aged; D000704:Analysis of Variance; D003864:Depression, Chemical; D006801:Humans; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D010455:Peptides; D011943:Receptors, Adrenergic, beta; D053607:Adrenomedullin