(Hypertension. 2000;36:501.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Leptin Attenuates Cardiac Contraction in Rat Ventricular Myocytes
Role of NO
From the Department of Pharmacology, Physiology, and Therapeutics (L.E.W., P.B.C, J.R.), University of North Dakota School of Medicine, Grand Forks; Department of Biomedical Engineering, College of Engineering, Wayne State University (M.W.N.), Detroit, Mich; the National Research Institute of Chinese Medicine (G.-J.W.), Taipei, Taiwan; and the Department of Pharmacological and Physiological Sciences (W.K.S.), St. Louis University School of Medicine, St. Louis, Mo.
Correspondence to Dr Jun Ren, Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, 501 N Columbia Rd, Grand Forks, ND 58203. E-mail jren{at}medicine.nodak.edu
Abstract—Obesity is commonly
associated with impaired myocardial contractile function. However, a
direct link between these 2 states has not yet been established. There
has been an indication that leptin, the product of the human
obesity gene, may play a role in obesity-related metabolic
and cardiovascular dysfunctions. The purpose of this
study was to determine whether leptin exerts any direct cardiac
contractile action that may contribute to altered myocardial function.
Ventricular myocytes were isolated from adult male
Sprague-Dawley rats. Contractile responses were evaluated by use of
video-based edge detection. Contractile properties analyzed in
cells electrically stimulated at 0.5 Hz included peak shortening, time
to 90% peak shortening, time to 90% relengthening, and
fluorescence intensity change. Leptin exhibited a
dose-dependent inhibition in myocyte shortening and intracellular
Ca2+ change, with maximal inhibitions of 22.4% and 26.2%,
respectively. Pretreatment with the NO synthase inhibitor
N
-nitro-L-arginine methyl
ester (L-NAME, 100 µmol/L) blocked leptin-induced inhibition of
both peak shortening and fluorescence intensity change. Leptin
also stimulated NO synthase activity in a time- and
concentration-dependent manner, as reflected in the dose-related
increase in NO accumulation in these cells. Addition of an NO donor
(S-nitroso-N-acetyl-penicillamine
[SNAP]) to the medium mimicked the effects of leptin administration.
In summary, this study demonstrated a direct action of leptin on
cardiomyocyte contraction, possibly through an increased NO
production. These data suggest that leptin may play a role in
obesity-related cardiac contractile dysfunction.
Key Words: hormones • myocytes • calcium • nitric oxide
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