Nitric oxide pathway presumably does not contribute to antianxiety and memory retrieval effects of losartan

Behav Pharmacol. 2017 Sep;28(6):420-427. doi: 10.1097/FBP.0000000000000311.

Abstract

Nitric oxide (NO) and angiotensin (AT) receptors have demonstrated well-established interactions in various physiological phenomena. AT1 receptors can play a part in stress-induced activation of the hypothalamic-pituitary-adrenal axis; also, angiotensinergic neurotransmission plays a pivotal role in stress-evoked physiological responses. On the basis of the stress-modulating characteristics of NO, AT1, and AT2 receptors, the present study evaluated the roles of NO and AT1 receptors in the attenuation of stress-induced anxiety-like behaviors after administration of losartan, an AT1 antagonist. Male Wistar rats were exposed to the communication stress box, using a novel method to induce physical or emotional stress, and losartan (10 mg/kg), losartan+L-NG-nitroargininemethyl ester (L-NAME), L-NAME (1, 10, and 100 mg/kg), and normal saline-treated groups were compared. Losartan had reduced behavioral changes induced by both types of stressor and enhanced memory retrieval. Anxiety-like behaviors were significantly attenuated by administration of losartan, to a greater extent in the emotional rather than physical stress group. None of the injected dosages of L-NAME reversed the antianxiety and memory retrieval effects of losartan. Our results indicate that losartan probably improves memory retrieval and lessens anxiety-like behaviors through mechanisms other than the NO pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensins / metabolism
  • Angiotensins / physiology
  • Animals
  • Anti-Anxiety Agents / metabolism
  • Behavior, Animal / drug effects
  • Hypertension
  • Hypothalamo-Hypophyseal System / drug effects
  • Hypothalamo-Hypophyseal System / metabolism
  • Imidazoles / pharmacology
  • Kidney / drug effects
  • Losartan / metabolism*
  • Losartan / pharmacology*
  • Male
  • Memory / drug effects
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / metabolism
  • Nitric Oxide / physiology
  • Pituitary-Adrenal System / drug effects
  • Pituitary-Adrenal System / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Angiotensin / drug effects
  • Receptors, Angiotensin / metabolism
  • Soluble Guanylyl Cyclase / drug effects
  • Soluble Guanylyl Cyclase / metabolism

Substances

  • Angiotensins
  • Anti-Anxiety Agents
  • Imidazoles
  • Receptors, Angiotensin
  • Nitric Oxide
  • Soluble Guanylyl Cyclase
  • Losartan
  • NG-Nitroarginine Methyl Ester