Centrally injected angiotensin II trans-synaptically activates angiotensin II-sensitive neurons in the anterior hypothalamic area of rats.
Previously, we have demonstrated that pressure-ejected application of angiotensin II onto some neurons in the anterior hypothalamic area (AHA) of rats increases their firing rate. In contrast, pressure application of the angiotensin AT1 receptor antagonist losartan onto AHA neurons blocked the basal firing of the neurons. To investigate possible participation of these AHA neurons in the brain angiotensin system, we examined whether intracerebroventricular injection of angiotensin II results in an activation of angiotensin II-sensitive neurons in the AHA of rats. Intracerebroventricular injection of angiotensin II increased the firing rate of AHA angiotensin II-sensitive neurons. The angiotensin II-induced increase of unit firing in AHA neurons was abolished by pressure application of losartan onto the same neurons. In addition, the angiotensin II-induced increase of firing in AHA neurons was abolished by pressure application of N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W7), a calmodulin inhibitor, onto the same neurons. Pressure application of W7 onto AHA neurons affected neither the basal firing rate nor the increase in unit firing induced by pressure application of angiotensin II onto the same neurons. Intracerebroventricular injection of the cholinergic agonist carbachol did not affect the firing rate of angiotensin II-sensitive neurons in the AHA. These findings suggest that intracerebroventricular injection of angiotensin II activates AHA angiotensin II-sensitive neurons via angiotensinergic inputs to the neurons.
Hagiwara
Yukihiko
Y
Department of Pharmacology, Showa Pharmaceutical University, Machida, Tokyo 194-8543, Japan.
Kubo
Takao
T
D000804:Angiotensin II / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D004558:Electric Stimulation; D007032:Hypothalamus, Anterior / Q000166:cytology* / Q000187:drug effects*; D007276:Injections, Intraventricular; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D047228:Angiotensin II Type 1 Receptor Blockers; D002147:Calmodulin; D018721:Muscarinic Agonists; D013449:Sulfonamides; D000804:Angiotensin II; C017967:W 7; D002217:Carbachol; D019808:Losartan