Chronic low-dose aspirin therapy attenuates reflex cutaneous vasodilation in middle-aged humans.
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.
Holowatz
Lacy A
LA
Department of Kinesiology, The Pennsylvania State University, University Park, Pennsylvania, USA. lma191@psu.edu
Kenney
W Larry
WL
D001241:Aspirin / Q000008:administration & dosage*; D001783:Blood Flow Velocity / Q000187:drug effects; D001808:Blood Vessels / Q000201:enzymology / Q000294:innervation; D001831:Body Temperature; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D005542:Forearm; D006801:Humans; D017078:Laser-Doppler Flowmetry; D008297:Male; D017551:Microdialysis; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009599:Nitroprusside / Q000008:administration & dosage; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D012018:Reflex / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000008:administration & dosage
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester