Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction

Jarrod D. Knudson, Ü Deniz Dincer, Cuihua Zhang, Albert N. Swafford, Ryoji Koshida, Andrea Picchi, Marta Focardi, Gregory M. Dick, Johnathan Tune

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Obesity is associated with marked increases in plasma leptin concentration, and hyperleptinemia is an independent risk factor for coronary artery disease. As a result, the purpose of this investigation was to test the following hypotheses: 1) leptin receptors are expressed in coronary endothelial cells; and 2) hyperleptinemia induces coronary endothelial dysfunction. RT-PCR analysis revealed that the leptin receptor gene is expressed in canine coronary arteries and human coronary endothelium. Furthermore, immunocytochemistry demonstrated that the long-form leptin receptor protein (ObRb) is present in human coronary endothelium. The functional effects of leptin were determined using pressurized coronary arterioles (ω-nitro-L- arginine methyl ester and was absent in obese Zucker rats. Intracoronary leptin dose-response experiments were conducted in anesthetized dogs. Normal and obese concentrations of leptin (0.1-3.0 μg/min ic) did not significantly change coronary blood flow or myocardial oxygen consumption; however, obese concentrations of leptin significantly attenuated the dilation to graded intracoronary doses of acetylcholine (0.3-30.0 μg/min). Additional experiments were performed in canine coronary rings, and relaxation to acetylcholine (6.25 nmol/1-6.25 μmol/l) was significantly attenuated by obese concentrations of leptin (625 pmol/l) but not by physiological concentrations of leptin (250 pmol/l). The major findings of this investigation were as follows: 1) the ObRb is present in coronary arteries and coupled to pharmacological, nitric oxide-dependent vasodilation; and 2) hyperleptinemia produces significant coronary endothelial dysfunction.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume289
Issue number1 58-1
DOIs
StatePublished - Jul 2005
Externally publishedYes

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Leptin Receptors
Leptin
Coronary Vessels
Acetylcholine
Endothelium
Canidae
Zucker Rats
Arterioles
Vasodilation
Oxygen Consumption
Coronary Artery Disease
Dilatation
Nitric Oxide
Endothelial Cells
Obesity
Immunohistochemistry
Pharmacology
Dogs
Polymerase Chain Reaction
Genes

Keywords

  • Coronary circulation
  • Endothelium
  • Metabolic syndrome
  • Microcirculation
  • Obesity

ASJC Scopus subject areas

  • Physiology

Cite this

Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction. / Knudson, Jarrod D.; Dincer, Ü Deniz; Zhang, Cuihua; Swafford, Albert N.; Koshida, Ryoji; Picchi, Andrea; Focardi, Marta; Dick, Gregory M.; Tune, Johnathan.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 289, No. 1 58-1, 07.2005.

Research output: Contribution to journalArticle

Knudson, Jarrod D. ; Dincer, Ü Deniz ; Zhang, Cuihua ; Swafford, Albert N. ; Koshida, Ryoji ; Picchi, Andrea ; Focardi, Marta ; Dick, Gregory M. ; Tune, Johnathan. / Leptin receptors are expressed in coronary arteries, and hyperleptinemia causes significant coronary endothelial dysfunction. In: American Journal of Physiology - Heart and Circulatory Physiology. 2005 ; Vol. 289, No. 1 58-1.
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