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

Ksenija Cankar, Zare Finderle, Martin Strucl

Institute of Physiology, School of Medicine, Zaloska 4, 1000 Ljubljana, Slovenia. Ksenija.cankar@mf.uni-lj.si

Microvascular research 2009 Mar

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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.

Citation

Ksenija Cankar, Zare Finderle, Martin Strucl. The effect of alpha-adrenoceptor agonists and L-NMMA on cutaneous postocclusive reactive hyperemia. Microvascular research. 2009 Mar;77(2):198-203