Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation in middle-aged humans

J Appl Physiol (1985). 2009 Feb;106(2):500-5. doi: 10.1152/japplphysiol.91215.2008. Epub 2008 Nov 26.

Abstract

Full expression of reflex cutaneous vasodilation is dependent on cyclooxygenase- (COX) and nitric oxide synthase- (NOS) dependent mechanisms. Low-dose aspirin therapy is widely prescribed to inhibit COX-1 in platelets for atherothrombotic prevention. We hypothesized that chronic COX inhibition with daily low-dose aspirin therapy (81 mg) would attenuate reflex vasodilation in healthy human skin. Two microdialysis fibers were placed in forearm skin of seven middle-aged (57 +/- 3 yr), normotensive, healthy humans with no preexisting cardiovascular disease, taking daily low-dose aspirin therapy (aspirin: 81 mg), and seven unmedicated, healthy, age-matched control (no aspirin, 55 +/- 3 yr) subjects, with one site serving as a control (Ringer) and the other NOS inhibited (NOS inhibited: 10 mM N(G)-nitro-l-arginine methyl ester). Red cell flux was measured over each site by laser-Doppler flowmetry, as reflex vasodilation was induced by increasing core temperature (oral temperature) 1.0 degrees C using a water-perfused suit. Cutaneous vascular conductance (CVC) was calculated (CVC = flux/mean arterial pressure) and normalized to maximal CVC (CVC(max); 28 mM sodium nitroprusside). CVC(max) was not affected by either aspirin or NOS inhibition. The plateau in cutaneous vasodilation during heating (change in oral temperature = 1.0 degrees C) was significantly attenuated in the aspirin group (aspirin: 25 +/- 3% CVC(max) vs. no aspirin: 50 +/- 7% CVC(max), P < 0.001 between groups). NOS inhibition significantly attenuated %CVC(max) in both groups (aspirin: 17 +/- 2% CVC(max), no aspirin: 23 +/- 3% CVC(max); P < 0.001 vs. control), but this attenuation was less in the no-aspirin treatment group (P < 0.001). This is the first observation that chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation through both COX- and NOS-dependent mechanisms.

Publication types

  • Controlled Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspirin / administration & dosage*
  • Blood Flow Velocity / drug effects
  • Blood Vessels / enzymology
  • Blood Vessels / innervation
  • Body Temperature
  • Cyclooxygenase Inhibitors / administration & dosage*
  • Drug Administration Schedule
  • Enzyme Inhibitors / administration & dosage
  • Female
  • Forearm
  • Humans
  • Laser-Doppler Flowmetry
  • Male
  • Microdialysis
  • Middle Aged
  • NG-Nitroarginine Methyl Ester / administration & dosage
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitroprusside / administration & dosage
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Prostaglandins / metabolism
  • Reflex / drug effects*
  • Regional Blood Flow / drug effects
  • Skin / blood supply*
  • Vasodilation / drug effects*
  • Vasodilator Agents / administration & dosage

Substances

  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Prostaglandins
  • Vasodilator Agents
  • Nitroprusside
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Prostaglandin-Endoperoxide Synthases
  • Aspirin
  • NG-Nitroarginine Methyl Ester