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.
Lenasi
Helena
H
Institute of Physiology, School of Medicine, University of Ljubljana, Zaloska 4, Ljubljana, Slovenia. helena.lenasi.ml@mf.uni-lj.si
Strucl
Martin
M
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