Effects of acute administration of doxazosin on fasting and postprandial haemodynamics and lipid metabolism in healthy subjects.
The selective alpha1 -adrenoceptor antagonist doxazosin has apparently beneficial effects on insulin sensitivity and on plasma lipid concentrations. In order to understand these effects better, we investigated the acute effects of doxazosin on adipose tissue and forearm blood flow and on postprandial lipid metabolism in healthy subjects. Nine subjects were studied in a balanced, placebo-controlled design. Pulse rate, blood pressure, forearm and subcutaneous adipose tissue blood flow were measured before and for 6 h after a mixed meal, with concomitant measurements of blood metabolites and insulin. Doxazosin increased pulse rate (p = 0.02) and forearm blood flow (p < 0.01 in fasting state), and decreased vascular resistance in forearm (p < 0.05 for fasting values) and subcutaneous abdominal adipose tissue (p = 0.04). Fasting plasma non-esterified fatty acid concentrations were increased by 40 % (p < 0.05). No other metabolic effects were detected. The effects on adipose tissue vascular resistance and lipolysis (reflected in elevated non-esterified fatty acid concentrations) were unexpected, as these are usually considered to be mediated by the balance of alpha2 - and beta-adrenoceptor activity in humans. We conclude that alpha1 -adrenoceptor activity may be more important in regulation of human lipid metabolism than previously recognized.
Ulahannan
T J
TJ
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Infirmary, Oxford, UK.
Karpe
F
F
Humphreys
S M
SM
Matthews
D R
DR
Frayn
K N
KN
D000273:Adipose Tissue / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects; D017292:Doxazosin / Q000008:administration & dosage*; D005215:Fasting; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D005542:Forearm / Q000098:blood supply; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D012039:Regional Blood Flow / Q000187:drug effects; D014280:Triglycerides / Q000097:blood
D000317:Adrenergic alpha-Antagonists; D005230:Fatty Acids, Nonesterified; D014280:Triglycerides; D017292:Doxazosin