Endothelium-Dependent NO-Mediated Vasodilation in Humans is Attenuated by Peripheral α₁-Adrenoceptor Activation

Abstract

Objectives

The release of nitric oxide is controlled by cholinergic and adrenergic receptors. Recent observations suggest that activation of β-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 N^G-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