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Endothelium-dependent NO-mediated vasodilation in humans is attenuated by peripheral a1-adrenoceptor activation

Authors Adriaan M Kamper, Anton JM de Craen, Rudi GJ Westendorp, Gerard J Blauw

Published 15 October 2005 Volume 2005:1(3) Pages 251—256


Adriaan M Kamper, Anton JM de Craen, Rudi GJ Westendorp, Gerard J Blauw

Departments of Gerontology & Geriatrics, Leiden University Medical Center, Leiden, The Netherlands

Objectives: The release of nitric oxide is controlled by cholinergic and adrenergic receptors. Recent observations suggest that activation of α-adrenoceptors can inhibit the release of nitric oxide. The aim of the present study was to examine the effect of α1- and α2-adrenoceptor activation on nitric oxide-mediated vasodilation.

Methodology: In a first set of experiments, the endothelium-dependent vasodilators acetylcholine (ACh), 5-hydroxytryptamine (5HT), and bradykinin (BK), and the nitric oxide donor sodium nitroprusside (SNP) were administered in a random order in the brachial artery together with saline, or the nonselective α-adrenoceptor agonists norepinephrine or clonidine, or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA). The infusions of saline, norepinephrine, clonidine, and L-NMMA started 10 minutes before the infusions of ACh, BK, 5HT, and SNP. In a second set of experiments, cumulative doses of ACh, BK, and 5HT were infused, in a random order, intra-arterially together with saline or the selective α1-adrenoceptor agonist methoxamine. The infusions of saline and methoxamine started 5 minutes before the infusions of ACh, BK, and 5HT. Forearm blood flow was measured using computerized venous occlusion plethysmography.

Results: ACh, 5HT, BK, and SNP induced a significant increase in forearm blood flow (p < 0.05 for all). These vasodilator responses were significantly attenuated by norepinephrine, clonidine, and L-NMMA (p < 0.05 for all), except for SNP. In the second set of experiments, all three endothelium-dependent vasodilators induced a dose-dependent vasodilation, which was significantly inhibited by methoxamine (p < 0.05).

Conclusion: These results show that endothelium-dependent nitric oxide-mediated vasodilation is inhibited by activation of peripheral α1-adrenoceptors.

Keywords: acetylcholine, α-adrenoceptors, bradykinin, 5-hydroxytryptamine, nitric oxide, strain-gauge plethysmography

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