Tonic angiotensinergic inputs to neurons in the anterior hypothalamic area of rats.
We have previously reported that microinjection of angiotensin II into the anterior hypothalamic area (AHA) produces a pressor response in rats and that the angiotensin AT1 receptor antagonist, losartan, similarly injected causes a depressor response in hypertensive rats. In this study, we examined whether endogenous angiotensins are involved in activation of neurons in the AHA. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Pressure-ejected application of angiotensin II and glutamate onto some neurons in the AHA increased their firing rate. The increase of unit firing induced by angiotensin II but not by glutamate was inhibited by losartan. Application of losartan alone inhibited the basal firing rate of angiotensin II-sensitive neurons in a concentration-dependent manner. Application of the angiotensin AT2 receptor antagonist, PD123319, did not affect the increase of unit firing induced by angiotensin II and the basal firing rate of angiotensin II-sensitive neurons. Pressure application of angiotensin I onto angiotensin II-sensitive neurons also increased firing rate and the increase of unit firing by angiotensin I was inhibited by the angiotensin converting enzyme inhibitor, captopril. Captopril alone inhibited the basal firing rate of angitensin II-sensitive neurons. Acetylcholine did not affect unit firing of angiotensin II-sensitive neurons, whereas it increased the firing rate of some angiotensin II-insensitive neurons in the AHA. Increases of blood pressure by intravenous phenylephrine completely inhibited the basal firing rate of angiotensin II-sensitive neurons. These findings suggest that some neurons in the AHA are tonically activated by endogenous angiotensins. It seems likely that newly synthesized angiotensins are used for the angiotensinergic transmission in the AHA.
Hagiwara
Yukihiko
Y
Department of Pharmacology, Showa Pharmaceutical University, Higasi-tamagawagakuen, Machida, Tokyo 194-8543, Japan.
Kubo
Takao
T
D000109:Acetylcholine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000809:Angiotensins / Q000378:metabolism*; D000818:Animals; D007025:Anterior Hypothalamic Nucleus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018698:Glutamic Acid / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010656:Phenylephrine / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D000889:Anti-Arrhythmia Agents; D007093:Imidazoles; D018727:Muscarinic Antagonists; D011725:Pyridines; D000804:Angiotensin II; C073402:PD 123319; D010656:Phenylephrine; D018698:Glutamic Acid; D000803:Angiotensin I; D002216:Captopril; D012601:Scopolamine; D019808:Losartan; D000109:Acetylcholine