The effect of alpha-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 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.
Cankar
Ksenija
K
Institute of Physiology, School of Medicine, Zaloska 4, 1000 Ljubljana, Slovenia. Ksenija.cankar@mf.uni-lj.si
Finderle
Zare
Z
Strucl
Martin
M
D000109:Acetylcholine / Q000008:administration & dosage; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D003000:Clonidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology*; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010656:Phenylephrine / Q000494:pharmacology; D012867:Skin / Q000098:blood supply* / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D010656:Phenylephrine; D019323:omega-N-Methylarginine; D019001:Nitric Oxide Synthase; D003000:Clonidine; D000109:Acetylcholine