Endothelium-dependent NO-mediated vasodilation in humans is attenuated by peripheral alpa1-adrenoceptor activation.
OBJECTIVE
The release of nitric oxide is controlled by cholinergic and adrenergic receptors. Recent observations suggest that activation of alpha-adrenoceptors can inhibit the release of nitric oxide. The aim of the present study was to examine the effect of alpha1- and alpha2-adrenoceptor activation on nitric oxide-mediated vasodilation.


METHODS
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 alpha-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 alpha1-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).


CONCLUSIONS
These results show that endothelium-dependent nitric oxide-mediated vasodilation is inhibited by activation of peripheral alpha1-adrenoceptors.
Kamper
Adriaan M
AM
Department of Gerontology, Leiden University Medical Center, Leiden, The Netherlands. a.m.kamper@lumc.nl
de Craen
Anton J M
AJ
Westendorp
Rudi G J
RG
Blauw
Gerard J
GJ
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D001916:Brachial Artery / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects; D012107:Research Design; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D008729:Methoxamine; D003000:Clonidine; D009638:Norepinephrine