Effects of Acute Administration of Doxazosin on Fasting and Postprandial Haemodynamics and Lipid Metabolism in Healthy Subjects

Abstract

The selective α₁-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 α₂- and β-adrenoceptor activity in humans. We conclude that α₁-adrenoceptor activity may be more important in regulation of human lipid metabolism than previously recognized.

Key words

α₁-Adrenoceptors - Adipose Tissue - Forearm - Blood Flow - Vascular Resistance - Non-Esterified Fatty Acids

References

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