The effect of nitric oxide synthase and cyclooxygenase inhibition on cutaneous microvascular reactivity

Eur J Appl Physiol. 2008 Aug;103(6):719-26. doi: 10.1007/s00421-008-0769-8. Epub 2008 May 31.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / administration & dosage
  • Adult
  • Biological Factors / metabolism
  • Blood Flow Velocity / drug effects
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / pharmacology*
  • Diclofenac / administration & dosage
  • Diclofenac / pharmacology*
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacology*
  • Epoprostenol / metabolism
  • Forearm
  • Humans
  • Injections, Intradermal
  • Iontophoresis
  • Laser-Doppler Flowmetry
  • Male
  • Microcirculation / drug effects
  • Microcirculation / enzymology
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type III / antagonists & inhibitors*
  • Nitric Oxide Synthase Type III / metabolism
  • Nitroprusside / administration & dosage
  • Regional Blood Flow / drug effects
  • Skin / blood supply*
  • Time Factors
  • Vasodilation / drug effects*
  • Vasodilator Agents / administration & dosage
  • omega-N-Methylarginine / administration & dosage
  • omega-N-Methylarginine / pharmacology*

Substances

  • Biological Factors
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Vasodilator Agents
  • endothelium-dependent hyperpolarization factor
  • Diclofenac
  • Nitroprusside
  • omega-N-Methylarginine
  • Nitric Oxide
  • Epoprostenol
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III
  • Acetylcholine