title: AT₁ receptor blockade in the lateral parabrachial nucleus reduces the effects of muscimol on sodium intake.
abstract: The blockade of the lateral parabrachial nucleus (LPBN) with GABA(A) receptor agonist muscimol induces robust hypertonic NaCl and water intake by rats. In the present study we investigated the effects of previous injections of losartan (AT(1) angiotensin receptor antagonist) into the LPBN on 0.3M NaCl and water intake induced by muscimol injected bilaterally in the same area in fluid replete rats and in rats treated with the diuretic furosemide combined with a low dose of the angiotensin-converting enzyme inhibitor captopril injected subcutaneously. Male Wistar rats with stainless steel cannulas implanted bilaterally into the LPBN were used. Bilateral injections of muscimol (0.5 nmol/0.2 μl, n=8) into the LPBN in fluid replete rats induced 0.3M NaCl intake (23.4±4.1 vs. saline: 0.4±0.4 ml/3h) and water intake (9.3±1.9 vs. saline: 0.7±0.4 ml/3h) and pre-treatment of the LPBN with losartan (50 μg/0.2 μl) reduced 0.3M NaCl intake (3.3±2.5 ml/3h) and water intake (4.0±2.9 ml/3h) induced by muscimol. In rats treated with furosemide+captopril, pre-treatment with losartan into the LPBN attenuated the increase of 0.3M NaCl intake produced by muscimol (12.8±5.3, vs. saline+muscimol: 36.7±6.7 ml/3h) without changing water intake. Therefore, the results suggest that deactivation of LPBN inhibitory mechanisms by muscimol injections into the LPBN is facilitated by endogenous angiotensin II acting on AT(1) receptors in the LPBN, which drives rats to ingest large amounts of hypertonic NaCl.
authors.affiliation: Department of Basic Science, School of Dentistry, UNESP, Univ. Estadual Paulista, Rodovia Marechal Rondom, km 527, 16018-805, Araçatuba, São Paulo, Brazil.
authors.forename: Camila Zambone C
authors.initials: CZ
authors.lastname: Da Silva
authors.forename: José V
authors.initials: JV
authors.lastname: Menani
authors.forename: João C
authors.initials: JC
authors.lastname: Callera
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects* / Q000502:physiology*; D005665:Furosemide / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D011149:Pons / Q000187:drug effects* / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012965:Sodium Chloride / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D058785:GABA-A Receptor Agonists; D009118:Muscimol; D012965:Sodium Chloride; D005665:Furosemide; D002216:Captopril; D019808:Losartan