Role of endogenous ET-1 in the regulation of myocardial blood flow in lean and obese humans.
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 micromol/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 approximately 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.
Mather
Kieren J
KJ
Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana, USA. kmather@iupui.edu
Lteif
Amale A
AA
Veeneman
Emily
E
Fain
Richard
R
Giger
Susan
S
Perry
Kevin
K
Hutchins
Gary D
GD
D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D018579:Patient Selection; D010456:Peptides, Cyclic / Q000494:pharmacology; D049268:Positron-Emission Tomography; D012044:Regression Analysis
D001786:Blood Glucose; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)