The effect of nitric oxide synthase and cyclooxygenase inhibition on cutaneous microvascular reactivity.
The role of nitric oxide (NO)- and prostacyclin (PGI(2))-independent mechanism, potentially attributable to endothelium-derived hyperpolarizing factor (EDHF), has not been extensively studied in human skin microcirculation. The aim of our study was to elucidate the contribution of the NO- and PGI(2)-independent mechanism to microvascular reactivity of cutaneous microcirculation. Skin perfusion was measured on the volar aspect of the forearm in 12 healthy male subjects (mean age 25.0 +/- 1.5), using laser Doppler (LD) fluxmetry. Combined endothelial nitric oxide synthase (eNOS) and cyclooxygenase (COX) inhibition was achieved by an intradermal injection (10 microl) of the eNOS inhibitor, L(omega)-monomethyl L-arginine (L-NMMA, 10 mM) and the COX inhibitor, diclofenac (10 mM); saline was injected as a control. LD flux was assessed at rest and after an iontophoretical application of acetylcholine (ACh, 1%), an endothelial agonist and sodium nitroprusside (SNP, 1%), an endothelium-independent agonist, respectively. Combined eNOS and COX inhibition had no effect on the baseline LDF (12.5 +/- 2.3 PU (perfusion units) in control vs. 10.9 +/- 1.8 PU in the treated site). On the other hand, the ACh-stimulated increase in LDF was significantly attenuated after eNOS and COX inhibition (390.5 +/- 43.5%), compared to the control (643.7 +/- 80.3% increase, t-test, P < 0.05). Nevertheless, at least 60% of ACh-mediated vasodilatation was preserved after combined eNOS and COX inhibition. eNOS and COX inhibition had no impact on the SNP-stimulated increase in LDF (768.8 +/- 70.5% in control vs. 733.5 +/- 54.6% in the treated site). These findings indicate that NO- and PGI(2)-independent mechanism plays an important role in the regulation of blood flow in the human skin microcirculation.
Institute of Physiology, School of Medicine, University of Ljubljana, Zaloska 4, Ljubljana, Slovenia. helena.lenasi.ml@mf.uni-lj.si
Helena
H
Lenasi
Martin
M
Strucl
D000109:Acetylcholine / Q000008:administration & dosage; D000328:Adult; D001685:Biological Factors / Q000378:metabolism; D001783:Blood Flow Velocity / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004008:Diclofenac / Q000008:administration & dosage / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011464:Epoprostenol / Q000378:metabolism; D005542:Forearm; D006801:Humans; D007271:Injections, Intradermal; D007478:Iontophoresis; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000201:enzymology; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage; D019323:omega-N-Methylarginine / Q000008:administration & dosage / Q000494:pharmacology*
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D004008:Diclofenac; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D011464:Epoprostenol; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000109:Acetylcholine