Intradermal angiotensin II administration attenuates the local cutaneous vasodilator heating response

Am J Physiol Heart Circ Physiol. 2008 Jul;295(1):H327-34. doi: 10.1152/ajpheart.00126.2008. Epub 2008 May 9.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Cutaneous
  • Adult
  • Angiotensin II / administration & dosage*
  • Angiotensin II Type 1 Receptor Blockers / administration & dosage
  • Angiotensin II Type 2 Receptor Blockers
  • Antioxidants / administration & dosage
  • Ascorbic Acid / administration & dosage
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / administration & dosage
  • Female
  • Hot Temperature*
  • Humans
  • Imidazoles / administration & dosage
  • Infusions, Parenteral
  • Losartan / administration & dosage
  • Male
  • Microdialysis
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Nitroarginine / administration & dosage
  • Pyridines / administration & dosage
  • Receptor, Angiotensin, Type 2 / metabolism
  • Regional Blood Flow
  • Skin / blood supply*
  • Skin Temperature*
  • Vasoconstrictor Agents / administration & dosage*
  • Vasodilation / drug effects*

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin II Type 2 Receptor Blockers
  • Antioxidants
  • Enzyme Inhibitors
  • Imidazoles
  • Pyridines
  • Receptor, Angiotensin, Type 2
  • Vasoconstrictor Agents
  • Angiotensin II
  • PD 123319
  • Nitroarginine
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Losartan
  • Ascorbic Acid