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This Article Full Text Full Text (PDF) All Versions of this Article: 107/4/1121    most recent 00750.2009v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Holowatz, L. A. Articles by Kenney, W. L. PubMed PubMed Citation Articles by Holowatz, L. A. Articles by Kenney, W. L.

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

¹Department of Kinesiology, ; ²Intercollege Program in Physiology, The Pennsylvania State University, Noll Laboratory, University Park, Pennsylvania

Submitted 13 July 2009 ; accepted in final form 6 August 2009

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°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 T_or 0.3°C; however, there was no difference between these sites with T_or 0.4°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.

skin blood flow; thermoregulation; prostaglandins; cyclooxygenase; nitric oxide