title: Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response.
abstract: 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 degrees 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 microg/l losartan, 10 mM nitro-l-arginine (NLA), or NLA + losartan was added to perfusate, and the heat response was remeasured; in another, 10 microM 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 microM) 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.
authors.affiliation: New York Medical College, Hawthorne, NY 10532, USA. julian_stewart@nymc.edu
authors.forename: Julian M
authors.initials: JM
authors.lastname: Stewart
authors.forename: Indu
authors.initials: I
authors.lastname: Taneja
authors.forename: Neeraj
authors.initials: N
authors.lastname: Raghunath
authors.forename: Debbie
authors.initials: D
authors.lastname: Clarke
authors.forename: Marvin S
authors.initials: MS
authors.lastname: Medow
mesh_terms: D000279:Administration, Cutaneous; D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage; D057912:Angiotensin II Type 2 Receptor Blockers; D000975:Antioxidants / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage; D007263:Infusions, Parenteral; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D017551:Microdialysis; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D019335:Nitroarginine / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage; D044139:Receptor, Angiotensin, Type 2 / Q000378:metabolism; D012039:Regional Blood Flow; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D057912:Angiotensin II Type 2 Receptor Blockers; D000975:Antioxidants; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019808:Losartan; D001205:Ascorbic Acid