Otro
Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring
Registro en:
The Journal of Nutrition, v. 145, n. 5, p. 907-914, 2015.
0022-3166
1684467594359403
Autor
Alves, José Luiz de Brito
Nogueira, Viviane Oliveira
Cavalcanti Neto, Marinaldo Pacífico
Leopoldino, Andréia Machado
Curti, Carlos
Colombari, Débora Simões de Almeida
Colombari, Eduardo
Wanderley, Almir Gonçalves
Leandro, Carol Gois
Zoccal, Daniel Breseghello
Costa-Silva, João Henrique da
Resumen
Background: Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms. Objectives: The aims of the study were to evaluate the effects of a low-protein (LP) diet during pregnancy and lactation on baseline sympathetic and respiratory activities and peripheral chemoreflex sensitivity in the rat offspring. Methods: Wistar rat dams were fed a control [normal-protein (NP); 17% protein] or an LP (8% protein) diet during pregnancy and lactation, and their male offspring were studied at 30 d of age. Direct measurements of baseline arterial blood pressure (ABP), heart rate (HR), and respiratory frequency (Rf) as well as peripheral chemoreflex activation (potassium cyanide: 0.04%) were recorded in pups while they were awake. In addition, recordings of the phrenic nerve (PN) and thoracic sympathetic nerve (tSN) activities were obtained from the in situ preparations. Hypoxia-inducible factor 1α (HIF-1α) expression was also evaluated in carotid bifurcation through a Western blotting assay. Results: At 30 d of age, unanesthetized LP rats exhibited enhanced resting Rf (P = 0.001) and similar ABP and HR compared with the NP rats. Despite their similar baseline ABP values, LP rats exhibited augmented low-frequency variability (∼91%; P = 0.01). In addition, the unanesthetized LP rats showed enhanced pressor (P = 0.01) and tachypnoeic (P = 0.03) responses to peripheral chemoreflex activation. The LP rats displayed elevated baseline tSN activity (∼86%; P = 0.02) and PN burst frequency (45%; P = 0.01) and amplitude (53%; P = 0.001) as well as augmented sympathetic (P = 0.01) and phrenic (P = 0.04) excitatory responses to peripheral chemoreflex activation compared with the NP group. Furthermore, LP rats showed an increase of ∼100% in HIF-1α protein density in carotid bifurcation compared with NP rats. Conclusion: Sympathetic-respiratory overactivity and amplified peripheral chemoreceptor responses, potentially through HIF-1α–dependent mechanisms, precede the onset of hypertension in juvenile rats exposed to protein undernutrition during gestation and lactation. Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)