Ketorolac alters blood flow during normothermia but not during hyperthermia in middle-aged human skin

J Appl Physiol (1985). 2009 Oct;107(4):1121-7. doi: 10.1152/japplphysiol.00750.2009. Epub 2009 Aug 6.


In young healthy humans full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase (COX)- and nitric oxide synthase (NOS)-dependent mechanisms. Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation potentially through both platelet and vascular COX-dependent mechanisms. We hypothesized the contribution of COX-dependent vasodilators to reflex cutaneous vasodilation during localized acute COX inhibition would be attenuated in healthy middle-aged humans due to a shift toward COX-dependent vasoconstrictors. Four microdialysis fibers were placed in forearm skin of 13 middle-aged (53 +/- 2 yr) normotensive healthy humans, serving as control (Ringer), COX-inhibited (10 mM ketorolac), NOS-inhibited (10 mM N(G)-nitro-l-arginine methyl ester), and combined NOS- and COX-inhibited sites. Red blood cell flux was measured over each site by laser-Doppler flowmetry as reflex vasodilation was induced by increasing oral temperature (T(or)) 1.0 degrees C using a water-perfused suit. Cutaneous vascular conductance was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVC(max); 28 mM sodium nitroprusside). CVC(max) was not affected by localized microdialysis drug treatment (P > 0.05). Localized COX inhibition increased baseline (18 +/- 3%CVC(max); P < 0.001) compared with control (9 +/- 1%CVC(max)), NOS-inhibited (7 +/- 1%CVC(max)), and combined sites (10 +/- 1%CVC(max)). %CVC(max) in the COX-inhibited site remained greater than the control site with DeltaT(or) < or = 0.3 degrees C; however, there was no difference between these sites with DeltaT(or) > or = 0.4 degrees C. NOS inhibition and combined COX and NOS inhibition attenuated reflex vasodilation compared with control (P < 0.001), but there was no difference between these sites. Localized COX inhibition with ketorolac significantly augments baseline CVC but does not alter the subsequent skin blood flow response to hyperthermia, suggesting a limited role for COX-derived vasodilator prostanoids in reflex cutaneous vasodilation and a shift toward COX-derived vasoconstrictors in middle-aged human skin.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Blood Flow Velocity / drug effects
  • Cyclooxygenase Inhibitors / administration & dosage
  • Cyclooxygenase Inhibitors / pharmacology*
  • Female
  • Forearm
  • Humans
  • Hypothermia / diagnostic imaging
  • Hypothermia / enzymology
  • Hypothermia / physiopathology*
  • Ketorolac / administration & dosage
  • Ketorolac / pharmacology*
  • Laser-Doppler Flowmetry
  • Male
  • Microdialysis
  • Middle Aged
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Regional Blood Flow / drug effects
  • Skin / blood supply*
  • Ultrasonography
  • Vasoconstriction / drug effects*
  • Vasodilation / drug effects*


  • Cyclooxygenase Inhibitors
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases
  • NG-Nitroarginine Methyl Ester
  • Ketorolac