Mecanismos angiotensinérgicos centrais e palatabilidade ao sódio

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Data

2022-05-31

Autores

Nascimento, Karoline Bernardes do

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Universidade Estadual Paulista (Unesp)

Resumo

The renin-angiotensin-aldosterone system is an important hormonal system activated in situations of hypovolemia and hypotension. Brain AT1R angiotensin II (ANG II) receptors activation stimulates thirst and sodium appetite, in addition vasoconstriction. On the other hand, acting on AT2R, ANG II promotes opposite effects, such as decrease in blood pressure and decrease in sodium appetite. Previous studies from our laboratory have shown the involvement of central AT1R in the increased sodium palatability in response to hypovolemia/sodium depletion. However, it is still unknown whether the blockade of AT2 receptors in sodium-depleted rats could change the hedonic shift induced by sodium depletion. Furthermore, it is also unknown whether central activation of angiotensinergic receptors could modulate NaCl palatability in normovolemic animals. Male Holtzman rats (290 g - 350 g), with guide cannula into the lateral ventricle (LV) and intraoral cannula (IO) were used. Rats had free access to water, 0.3 M NaCl and food, until immediately before the experiments. Palatability to 0.3 M NaCl was evaluated using the taste reactivity test (TRT), which determines the frequency of orofacial reactions in response to a flavor directly infused into the oral cavity. Sodium depletion was induced by treatment with furosemide diuretic (10 mg/kg, 1,0 ml, s.c.) or control treatment (furosemide vehicle: 0.9% NaCl with pH adjusted to 9.0, 1,0 ml, s.c.), with free access to water associated with a sodium-deficient diet and removal of sodium solution for 24 h. In satiated animals, without any previous treatment, the frequency of hedonic and aversive responses to IO infusion of 0.3 M NaCl (1,0 ml/min) was not altered after ANG II injection into the LV. Previous losartan (ANG II AT1 receptor antagonist) injection in the LV abolished the ANG II dipsogenic response. After access to water, there was also no change in the number of hedonic and aversive responses to NaCl in animals treated with saline + ANG II or losartan + ANG II. Regarding AT2 receptors, previous administration of PD123319 (ANG II AT2 receptor antagonist) did not alter the dipsogenic response of central ANG II. There were also no changes in the frequency of hedonic and aversive responses between treatments throughout the experiment. These results suggest that central activation of AT1 angiotensinergic receptors alone is not sufficient to alter the palatability of hypertonic NaCl. However, further studies using higher doses of ANG II and/or more dilute NaCl solutions are needed to complement the present results. In sodium-depleted rats (n = 12), there was an increase in 0.3 M NaCl intake during the sodium appetite test according to previous literature. However, the number of animals with confirmed injections into the VL was only 2, which is insignificant to assess the possible effect of AT2 blockade on ingestion and increased palatability to 0.3 M NaCl induced by sodium depletion. Further studies are needed to elucidate this question.
A ingestão de água e de alimentos que contêm sódio é uma resposta comportamental fundamental para um indivíduo repor suas necessidades de água e NaCl. Esses comportamentos ingestivos são regulados por mecanismos ativados em situações de hipovolemia e alterações de osmolaridade plasmática. O sistema renina-angiotensinaaldosterona (SRAA) é um importante sistema hormonal, ativado em situações de hipovolemia, para o controle da pressão arterial e ingestão de água e apetite ao sódio. Por outro lado, o consumo excessivo de sal tem sido associado ao desenvolvimento ou agravamento de doenças crônicas, incluindo a hipertensão. Estudos prévios de nosso laboratório mostraram o envolvimento de receptores angiotensinérgicos AT1 centrais no aumento da palatabilidade ao sódio em resposta a depleção de sódio. Contudo, ainda era desconhecido se apenas a ativação central de receptores angiotensinérgicos poderia alterar a palatabilidade ao NaCl em animais normovolêmicos. Assim sendo, o objetivo foi investigar se ativação central de receptores angiotensinérgicos AT1 poderia modular a palatabilidade ao NaCl em animais normovolêmicos, sem quaisquer prévios tratamentos como restrição hídrica ou dieta deficiente de sódio. Além disso, também foi investigado se os receptores AT2 centrais de angiotensina II estariam envolvidos no desvio da palatabilidade ao sódio induzido por depleção de sódio.

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Palavras-chave

Angiotensins, Thirst, Sodium, Taste, Drinking behavior, Angiotensinas, Sede, Sódio, Paladar, Comportamento de ingestão de líquido

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