The effect of alpha-adrenoceptor agonists and L-NMMA on cutaneous postocclusive reactive hyperemia.

Abstract

Postocclusive reactive hyperemia (PRH) is considered to be a locally mediated vascular reaction independent of sympathetic activity. However, experiments on animal vascular preparations have shown that alpha(2)-adrenoceptor activity interferes with the production of endothelium-derived nitric oxide (NO) that has been found to play an important role in the PRH response. We attempted to elucidate the role of endothelium-derived NO in the cutaneous PRH response. Especially, we aimed to clarify the interference of the alpha-adrenoceptor activity with NO mechanism in cutaneous microcirculation. We studied the effect of intradermal microinjection of the NO synthase inhibitor L-NMMA alone, alpha(1)-agonist phenylephrine alone, alpha(2)-agonist clonidine alone and L-NMMA in combination with each alpha-agonist. The effect of the saline solution injection was used as a reference value. Laser-Doppler flux was monitored in 11 healthy volunteers before and after a 4-minute and an 8-minute occlusion of digital arteries. The application of L-NMMA significantly reduced resting LD-flux (p<0.05) only in combination with alpha(2)-agonist but not alpha(1)-agonist. The application of L-NMMA alone changed the time in which LD flux reached half of the preocclusive value during the PRH response (T/2) only after 4-minute (p<0.05) but not after an 8-minute occlusion. Phenylephrine (alpha(1)-agonist) alone shortened (p<0.05), while clonidine (alpha(2)-agonist) alone prolonged T/2 (p<0.05) of 8-minute PRH. The combined application of L-NMMA and clonidine abolished the effect of clonidine alone on 8-minute PRH. In contrast, the combination of L-NMMA and phenylephrine did not cause any change of the PRH response when compared to the injection of phenylephrine alone. Our finding is consistent with the hypothesis that alpha(2)-adrenoceptor activity (in the condition of maximal agonist stimulation) could interfere with NO mechanisms in cutaneous microcirculation, probably by increasing NO production.

• Authors: Ksenija Cankar, Zare Finderle, Martin Strucl
• Journal: Microvascular research (Microvasc Res) Vol. 77 Issue 2 Pg. 198-203 (Mar 2009) ISSN: 1095-9319 [Electronic] United States
• PMID: 19028506 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic alpha-Agonists
• Enzyme Inhibitors
• Phenylephrine
• omega-N-Methylarginine
• Nitric Oxide Synthase
• Clonidine
• Acetylcholine

Topics

• Acetylcholine (administration & dosage)
• Adrenergic alpha-Agonists (pharmacology)
• Adult
• Clonidine (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Female
• Humans
• Hyperemia (physiopathology)
• Iontophoresis
• Laser-Doppler Flowmetry
• Male
• Microcirculation (drug effects, physiology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Phenylephrine (pharmacology)
• Skin (blood supply, drug effects, innervation, physiopathology)
• omega-N-Methylarginine (pharmacology)