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

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 of-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 LID 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. (c) 2008 Elsevier Inc. All rights reserved.