Role of endogenous ET-1 in the regulation of myocardial blood flow in lean and obese humans

Kieren Mather, Amale Lteif, Emily Veeneman, Richard Fain, Susan Giger, Kevin Perry, Gary Hutchins

Research output: Contribution to journalArticle

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Abstract

Endothelin is an important determinant of peripheral vascular tone, and increased endogenous endothelin activity contributes to peripheral vascular dysfunction in human obesity. The contributions of endothelin to the regulation of coronary vascular tone in health in humans have not been well studied. We hypothesized that the contribution of endothelin to the regulation of myocardial perfusion would be augmented in human obesity. Using NH 3 ammonia positron emission tomography (PET), we measured myocardial perfusion under resting and adenosine-stimulated conditions on two separate days, with and without concurrent exposure to BQ123, an antagonist of type A endothelin receptors (1 νmol/min IV beginning 90 min before measurement). We studied 10 lean and 9 obese subjects without hypertension, hyperlipidemia, or diabetes mellitus. We observed a BQ123-induced increase in resting myocardial perfusion of ∼40%, not different between lean and obese subjects (BQ123-induced increase in flow: lean 0.12 0.20, obese 0.32 0.51 ml/g/min, P = 0.02 BQ123 effect, P = 0.27 comparing response across groups). Although basal flow rates varied by region of the myocardium, the BQ123 effect was seen in all regions. BMI and cholesterol were significantly related to BQ123-induced increases in basal tone in multivariable analysis. There was no baseline difference in the adenosine-stimulated increase in blood flow between lean and obese subjects, and BQ123 failed to augment these responses in either group. These observations suggest that endothelin is an important contributor to the regulation of myocardial perfusion under resting conditions in healthy lean and obese humans, with increased contributions in proportion to increasing obesity.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalObesity
Volume18
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Endothelins
Perfusion
Blood Vessels
Obesity
Adenosine
Endothelin A Receptors
cyclo(Trp-Asp-Pro-Val-Leu)
Hyperlipidemias
Ammonia
Positron-Emission Tomography
Myocardium
Diabetes Mellitus
Cholesterol
Hypertension
Health

ASJC Scopus subject areas

  • Endocrinology
  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Role of endogenous ET-1 in the regulation of myocardial blood flow in lean and obese humans. / Mather, Kieren; Lteif, Amale; Veeneman, Emily; Fain, Richard; Giger, Susan; Perry, Kevin; Hutchins, Gary.

In: Obesity, Vol. 18, No. 1, 01.2010, p. 63-70.

Research output: Contribution to journalArticle

Mather, Kieren ; Lteif, Amale ; Veeneman, Emily ; Fain, Richard ; Giger, Susan ; Perry, Kevin ; Hutchins, Gary. / Role of endogenous ET-1 in the regulation of myocardial blood flow in lean and obese humans. In: Obesity. 2010 ; Vol. 18, No. 1. pp. 63-70.
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