Envolvimento da área septal medial no controle da ingestão de água e sódio
Carregando...
Data
2022-12-16
Autores
Santana, Carolina Ortiz
Título da Revista
ISSN da Revista
Título de Volume
Editor
Universidade Estadual Paulista (Unesp)
Resumo
Angiotensina II (ANG II) atuando em áreas prosencefálicas e aldosterona por suas ações no
bulbo são importantes hormônios estimuladores da ingestão de sódio. As ações estimuladoras
destes hormônios são contrabalanceadas pela atividade de mecanismos inibitórios como
aqueles do Núcleo Parabraquial Lateral (NPBL). O balanço destas duas ações opostas é que
determina se a ingestão de sódio deve ocorrer ou não. Uma área prosencefálica que tem um
papel bem definido na ingestão de água, mas ainda pouco estudada para a ingestão de sódio é
a Área Septal Medial (ASM). Porém, resultados preliminares do nosso laboratório mostraram
que receptores angiotensinérgicos AT1 da ASM parecem ser importantes para a ingestão de
sódio. Mas como já demonstrado para outras áreas cerebrais como o Órgão Subfornical (OSF),
também no caso da ASM, a ingestão de sódio parece ser fortemente inibida pelos mecanismos
inibitórios do NPBL e só ocorre quando estes mecanismos inibitórios são bloqueados pela
injeção de moxonidina (agonista adrenérgico α2/imidazólico) no NPBL. Portanto, os objetivos
do presente estudo foram investigar o possível envolvimento de mecanismos
angiotensinérgicos e/ou colinérgicos da ASM no controle da ingestão de sódio produzida por
diversos estímulos como depleção de sódio, furosemida + captopril subcutaneamente (sc) em
ratos que receberem injeções moxonidina no NPBL ou em ratos saciados que receberem
injeções de muscimol (agonista GABAA) no NPBL. Foram utilizados ratos Holtzman com peso
em torno de 300 g mantidos em gaiolas individuais com ração Socil, água e NaCl 0,3 M
disponíveis. Os animais tiveram implante de cânulas de aço inoxidável no NPBL
(bilateralmente) e na ASM. As injeções centrais foram feitas utilizando-se uma seringa
Hamilton (5 μl), num volume de 0,2 ou 0,5 μl. Os resultados obtidos mostraram que injeções
bilaterais de muscimol (0,5 nmol/0,2 µl) no NPBL em ratos tratados com injeção de salina na
ASM aumentaram significativamente a ingestão de NaCl 0,3 M (33,2 ± 11,4, vs. salina ASM +
salina NPBL: 0,04 ± 0,03 mL/240 min) e de água (9,3 ± 3,6, vs. salina ASM + salina NPBL:
0,6 ± 0,3 mL/240 min). As injeções de atropina (2 nmol/0,5 µl) ou losartana (10 µg/0,5 µl) na
ASM reduziram significativamente a ingestão de NaCl 0,3 M (13,8 ± 3,7 e 10,9 ± 3,1 mL/240
min, respectivamente), mas não a ingestão de água em ratos tratados com muscimol no NPBL.
Em ratos tratados com furosemida + captopril sc que receberam injeção de salina na ASM, as
injeções bilaterais de moxonidina (0,5 nmol/0,2 µl) no NPBL aumentaram significativamente
a ingestão de NaCl 0,3 M (30,9 ± 4,7, vs. salina ASM + veículo NPBL: 3,0 ± 1,0 mL/120 min)
e de água (18,4 ± 2,6, vs. salina ASM + veículo NPBL: 9,6 ± 1,2 mL/120 min). As injeções de
losartana (10 µg/0,5 µl) na ASM reduziram significativamente a ingestão de NaCl 0,3 M e de
água em ratos tratados furosemida + captopril que receberam injeções de moxonidina no NPBL
(13,4 ± 4,8 e 12,6 ± 3,1 mL/120 min, respectivamente). Porém, a injeção de atropina na ASM
não modificou a ingestão de NaCl 0,3 M e água em ratos tratados com furosemida + captopril
combinado com moxonidina no NPBL (30,7 ± 6,6 e 12,9 ± 4,1 mL/120 min, respectivamente).
Em conclusão, os presentes resultados sugerem que mecanismos angiotensinérgicos AT1 e
colinérgicos muscarínicos da ASM fazem parte dos mecanismos facilitatórios da ingestão de
NaCl. Adicionalmente, os resultados sugerem que os mecanismos angiotensinérgicos AT1 e
colinérgicos muscarínicos da ASM são fortemente inibidos pelos mecanismos inibitórios da
ingestão de NaCl do NPBL.
Angiotensin II (ANG II) acting in forebrain areas and aldosterone by their actions in the medulla are important hormones that stimulate sodium intake. The stimulatory actions of these hormones are counterbalanced by the activity of inhibitory mechanisms such as those of the Lateral Parabrachial Nucleus (LPBN). The balance between these two opposite actions is what determines whether sodium intake should occur or not. A forebrain area that has a well-defined role in water intake, but still poorly studied for sodium intake is the Medial Septal Area (MSA). However, preliminary results from our laboratory showed that MSA AT1 angiotensinergic receptors appear to be important for sodium intake. But as already demonstrated for other brain areas such as the Subfornical Organ (SFO), also in the case of MSA, sodium intake seems to be strongly inhibited by the LPBN inhibitory mechanisms and only occurs when these inhibitory mechanisms are blocked by the injection of moxonidine (α2-adrenergic/imidazole agonist) in LPBN. Therefore, the objectives of the present study were to investigate the possible involvement of angiotensinergic and/or cholinergic mechanisms of MSA in the control of sodium intake produced by various stimulus such as sodium depletion, furosemida + captopril subcutaneously (sc) in rats receiving moxonidine injections in the LPBN or in satiated rats that receive injections of muscimol (GABAA agonist) into the LPBN. Male Holtzman rats weighing around 300 g were housed in individual cages with Socil chow, water and 0.3 M NaCl available. The animals had stainless steel cannulas implanted in the LPBN (bilaterally) and in the MSA. Central injections were made using a Hamilton syringe (5 µl), in a volume of 0.2 or 0.5 µl. The results obtained showed that bilateral injections of muscimol (0.5 nmol/0.2 µl) into the LPBN in rats treated with saline injection into the MSA significantly increased the intake of 0.3 M NaCl (33.2 ± 11.4, vs. saline MSA + saline LPBN: 0.04 ± 0.03 mL/240 min) and water (9.3 ± 3.6, vs. saline MSA + saline LPBN: 0.6 ± 0.3 mL/240 min). Injections of atropine (2 nmol/0.5 µl) or losartan (10 µg/0.5 µl) into the MSA significantly reduced 0.3 M NaCl and water intake in rats treated with muscimol into the LPBN (13.8 ± 3.7 and 10.9 ± 3.1 mL/240 min, respectively). In rats treated with furosemida + captopril that received saline injection into the MSA, bilateral injections of moxonidine (0.5 nmol/0.2 µl) into LPBN significantly increased 0.3 M NaCl intake (30.9 ± 4.7, vs. saline MSA + vehicle LPBN: 3.0 ± 1.0 mL/120 min) and water (18.4 ± 2.6 vs. saline MSA + vehicle LPBN: 9.6 ± 1.2 mL /120 min). Losartan injections (10 µg/0.5 µl) into the MSA significantly reduced 0.3 M NaCl and water intake in furosemida + captopril treated rats that received moxonidine injections into the LPBN (13.4 ± 4.8 and 12.6 ± 3.1 mL/120 min, respectively). However, the injection of atropine into the MSA did not modify the ingestion of 0.3 M NaCl and water in rats treated with furosemida + captopril combined with moxonidine into the LPBN (30.7 ± 6.6 and 12.9 ± 4.1 mL/ 120 min, respectively). In conclusion, the present results suggest that AT1 angiotensinergic and muscarinic cholinergic mechanisms of the MSA are part of the facilitatory mechanisms for NaCl ingestion. Additionally, the results suggest that the AT1 angiotensinergic and muscarinic cholinergic mechanisms of the MSA are strongly inhibited by the LPBN inhibitory mechanisms for NaCl ingestion.
Angiotensin II (ANG II) acting in forebrain areas and aldosterone by their actions in the medulla are important hormones that stimulate sodium intake. The stimulatory actions of these hormones are counterbalanced by the activity of inhibitory mechanisms such as those of the Lateral Parabrachial Nucleus (LPBN). The balance between these two opposite actions is what determines whether sodium intake should occur or not. A forebrain area that has a well-defined role in water intake, but still poorly studied for sodium intake is the Medial Septal Area (MSA). However, preliminary results from our laboratory showed that MSA AT1 angiotensinergic receptors appear to be important for sodium intake. But as already demonstrated for other brain areas such as the Subfornical Organ (SFO), also in the case of MSA, sodium intake seems to be strongly inhibited by the LPBN inhibitory mechanisms and only occurs when these inhibitory mechanisms are blocked by the injection of moxonidine (α2-adrenergic/imidazole agonist) in LPBN. Therefore, the objectives of the present study were to investigate the possible involvement of angiotensinergic and/or cholinergic mechanisms of MSA in the control of sodium intake produced by various stimulus such as sodium depletion, furosemida + captopril subcutaneously (sc) in rats receiving moxonidine injections in the LPBN or in satiated rats that receive injections of muscimol (GABAA agonist) into the LPBN. Male Holtzman rats weighing around 300 g were housed in individual cages with Socil chow, water and 0.3 M NaCl available. The animals had stainless steel cannulas implanted in the LPBN (bilaterally) and in the MSA. Central injections were made using a Hamilton syringe (5 µl), in a volume of 0.2 or 0.5 µl. The results obtained showed that bilateral injections of muscimol (0.5 nmol/0.2 µl) into the LPBN in rats treated with saline injection into the MSA significantly increased the intake of 0.3 M NaCl (33.2 ± 11.4, vs. saline MSA + saline LPBN: 0.04 ± 0.03 mL/240 min) and water (9.3 ± 3.6, vs. saline MSA + saline LPBN: 0.6 ± 0.3 mL/240 min). Injections of atropine (2 nmol/0.5 µl) or losartan (10 µg/0.5 µl) into the MSA significantly reduced 0.3 M NaCl and water intake in rats treated with muscimol into the LPBN (13.8 ± 3.7 and 10.9 ± 3.1 mL/240 min, respectively). In rats treated with furosemida + captopril that received saline injection into the MSA, bilateral injections of moxonidine (0.5 nmol/0.2 µl) into LPBN significantly increased 0.3 M NaCl intake (30.9 ± 4.7, vs. saline MSA + vehicle LPBN: 3.0 ± 1.0 mL/120 min) and water (18.4 ± 2.6 vs. saline MSA + vehicle LPBN: 9.6 ± 1.2 mL /120 min). Losartan injections (10 µg/0.5 µl) into the MSA significantly reduced 0.3 M NaCl and water intake in furosemida + captopril treated rats that received moxonidine injections into the LPBN (13.4 ± 4.8 and 12.6 ± 3.1 mL/120 min, respectively). However, the injection of atropine into the MSA did not modify the ingestion of 0.3 M NaCl and water in rats treated with furosemida + captopril combined with moxonidine into the LPBN (30.7 ± 6.6 and 12.9 ± 4.1 mL/ 120 min, respectively). In conclusion, the present results suggest that AT1 angiotensinergic and muscarinic cholinergic mechanisms of the MSA are part of the facilitatory mechanisms for NaCl ingestion. Additionally, the results suggest that the AT1 angiotensinergic and muscarinic cholinergic mechanisms of the MSA are strongly inhibited by the LPBN inhibitory mechanisms for NaCl ingestion.
Descrição
Palavras-chave
NPBL, ASM, Ingestão, angiotensina, atropina, losartana, moxonidina, muscimol, LPBN, MSA, Ingestion, ANG II, losartan, moxonidine