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Am J Physiol Heart Circ Physiol 295: H327-H334, 2008. First published May 9, 2008; doi:10.1152/ajpheart.00126.2008
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Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

Julian M. Stewart, Indu Taneja, Neeraj Raghunath, Debbie Clarke, and Marvin S. Medow

New York Medical College, Hawthorne, New York

Submitted 6 February 2008 ; accepted in final form 6 May 2008

The vasodilation response to local cutaneous heating is nitric oxide (NO) dependent and blunted in postural tachycardia but reversed by angiotensin II (ANG II) type 1 receptor (AT1R) blockade. We tested the hypothesis that a localized infusion of ANG II attenuates vasodilation to local heating in healthy volunteers. We heated the skin of a calf to 42°C and measured local blood flow to assess the percentage of maximum cutaneous vascular conductance (%CVCmax) in eight healthy volunteers aged 19.5–25.5 years. Initially, two experiments were performed; in one, Ringer solution was perfused in three catheters, the response to heating was measured, 2 µg/l losartan, 10 mM nitro-L-arginine (NLA), or NLA + losartan was added to perfusate, and the heat response was remeasured; in another, 10 µM ANG II was given, the heat response was measured, losartan, NLA, or NLA + losartan was added to ANG II, and the heat response was reassessed. The heat response decreased with ANG II, particularly the plateau phase (47 ± 5 vs. 84 ± 3 %CVCmax). Losartan increased baseline conductance in both experiments (from 8 ± 1 to 20 ± 2 and 12 ± 1 to 24 ± 3). Losartan increased the ANG II response (83 ± 4 vs. 91 ± 6 in Ringer). NLA decreased both angiotensin and Ringer responses (31 ± 4 vs. 43 ± 3). NLA + losartan blunted the Ringer response (48 ± 2), but the ANG II response (74 ± 5) increased. In a second set of experiments, we used dose responses to ANG II (0.1 nM to 10 µM) with and without NLA + losartan to confirm graded responses. Sodium ascorbate (10 mM) restored the ANG II-blunted heating plateau. NO synthase and AT1R inhibition cause an NO-independent angiotensin-mediated vasodilation with local heating. ANG II mediates the AT1R blunting of local heating, which is not exclusively NO dependent, and is improved by antioxidant supplementation.

lasers; conductance; skin



Address for reprint requests and other correspondence: J. M. Stewart, The Center for Pediatric Hypotension, Ste. 3050, 19 Bradhurst Ave., New York Medical College, Hawthorne, NY 10532 (e-mail: julian_stewart{at}nymc.edu)







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