Intracerebroventricular injection of losartan inhibits angiotensin II-sensitive neurons via GABA inputs in the anterior hypothalamic area of rats.
Previously, we have demonstrated that pressure-ejected application of angiotensin II and losartan, an angiotensin AT1 receptor antagonist, onto some neurons in the anterior hypothalamic area (AHA) of the rat increases and decreases, respectively, the basal firing rate of the neurons. To investigate possible participation of these AHA neurons in the brain angiotensin system, we examined whether intracerebroventricular injection of the angiotensin AT1 receptor antagonist losartan inhibits the neuronal activity of angiotensin II-sensitive neurons via GABA inputs in the AHA of rats. Intracerebroventricular injection of losartan decreased the firing rate of AHA angiotensin II-sensitive neurons. However, the intracerebroventricular injection of losartan did not affect the increase in firing rate of AHA angiotensin II-sensitive neurons induced by pressure application of angiotensin II onto the same neurons, although losartan similarly injected abolished the increase in firing rate of AHA angiotensin II-sensitive neurons induced by intracerebroventricular injection of angiotensin II. The losartan-induced decrease of unit firing in AHA neurons was abolished by pressure application of the GABAA receptor antagonist bicuculline onto the same neurons. Bicuculline itself did not affect the basal firing rate of AHA neurons. These findings suggest that intracerebroventricular injection of losartan inhibits AHA angiotensin II-sensitive neurons via GABA inputs to the neurons.
Hagiwara
Yukihiko
Y
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Kubo
Takao
T
D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000187:drug effects; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000187:drug effects*; D001640:Bicuculline / Q000008:administration & dosage; D018756:GABA Antagonists / Q000008:administration & dosage; D007276:Injections, Intraventricular; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D047228:Angiotensin II Type 1 Receptor Blockers; D018756:GABA Antagonists; D000804:Angiotensin II; D005680:gamma-Aminobutyric Acid; D019808:Losartan; D001640:Bicuculline