Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

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 (AT 1 R) 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 (%CVC max ) 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 %CVC max ). 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 AT 1 R inhibition cause an NO-independent angiotensin-mediated vasodilation with local heating. ANG II mediates the AT 1 R 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 )