Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring.
BACKGROUND
Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms.


OBJECTIVE
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.


CONCLUSIONS
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.
Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitoria de Santo Antão, Pernambuco, Brazil;
José L
JL
de Brito Alves
Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitoria de Santo Antão, Pernambuco, Brazil;
Viviane O
VO
Nogueira
Departments of Physics and Chemistry and Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
Marinaldo P
MP
Cavalcanti Neto
Departments of Physics and Chemistry and Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
Andréia M
AM
Leopoldino
Departments of Physics and Chemistry and Clinical Analyses, Toxicology and Food Sciences, School of Pharmaceutical Sciences, University of São Paulo, Ribeirão Preto, São Paulo, Brazil;
Carlos
C
Curti
Department of Physiology and Pathology, School of Dentistry of Araraquara, São Paulo State University, Araraquara, São Paulo, Brazil; and.
Débora S A
DS
Colombari
Department of Physiology and Pathology, School of Dentistry of Araraquara, São Paulo State University, Araraquara, São Paulo, Brazil; and.
Eduardo
E
Colombari
Department of Physiology and Pharmacology, Federal University of Pernambuco, Pernambuco, Brazil.
Almir G
AG
Wanderley
Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitoria de Santo Antão, Pernambuco, Brazil;
Carol G
CG
Leandro
Department of Physiology and Pharmacology, Federal University of Pernambuco, Pernambuco, Brazil.
Daniel B
DB
Zoccal
Department of Physical Education and Sport Sciences, Federal University of Pernambuco, Vitoria de Santo Antão, Pernambuco, Brazil; joao.hcsilva@ufpe.br.
João H
JH
Costa-Silva
D000818:Animals; D001724:Birth Weight; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002628:Chemoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D018753:Diet, Protein-Restricted / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000209:etiology / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007774:Lactation; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D017933:Peripheral Nervous System / Q000473:pathology / Q000503:physiopathology*; D010791:Phrenic Nerve / Q000473:pathology / Q000503:physiopathology; D011247:Pregnancy; D058246:Prehypertension / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D017208:Rats, Wistar; D012137:Respiratory System / Q000473:pathology / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000473:pathology / Q000503:physiopathology*; D013900:Thoracic Nerves / Q000473:pathology / Q000503:physiopathology
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
hypertension; hypoxia-inducible factor 1 α; peripheral chemoreflex; protein undernutrition; sympathetic overactivity