Angiotensin II (de)sensitization: Fluid intake studies with implications for cardiovascular control

Physiol Behav. 2016 Aug 1;162:141-6. doi: 10.1016/j.physbeh.2016.01.020. Epub 2016 Jan 19.

Abstract

Cardiovascular disease is the leading cause of death worldwide and hypertension is the most common risk factor for death. Although many anti-hypertensive pharmacotherapies are approved for use in the United States, rates of hypertension have increased over the past decade. This review article summarizes a presentation given at the 2015 meeting of the Society for the Study of Ingestive Behavior. The presentation described work performed in our laboratory that uses angiotensin II-induced drinking as a model system to study behavioral and cardiovascular effects of the renin-angiotensin system, a key component of blood pressure regulation, and a common target of anti-hypertensives. Angiotensin II (AngII) is a potent dipsogen, but the drinking response shows a rapid desensitization after repeated injections of AngII. This desensitization appears to be dependent upon the timing of the injections, requires activation of the AngII type 1 (AT1) receptor, requires activation of mitogen-activated protein (MAP) kinase family members, and involves the anteroventral third ventricle (AV3V) region as a critical site of action. Moreover, the response does not appear to be the result of a more general suppression of behavior, a sensitized pressor response to AngII, or an aversive state generated by the treatment. More recent studies suggest that the treatment regimen used to produce desensitization in our laboratory also prevents the sensitization that occurs after daily bolus injections of AngII. Our hope is that these findings can be used to support future basic research on the topic that could lead to new developments in treatments for hypertension.

Keywords: Angiotensin; Desensitization; Hypertension; Saline intake; Sensitization; Water intake.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiotensin II / pharmacology*
  • Animals
  • Cardiovascular System / drug effects*
  • Drinking / drug effects*
  • Drug Tolerance
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Signal Transduction / drug effects
  • Vasoconstrictor Agents / pharmacology*

Substances

  • Vasoconstrictor Agents
  • Angiotensin II
  • Mitogen-Activated Protein Kinase Kinases