Maternal protein restriction increases respiratory and sympathetic activities and sensitizes peripheral chemoreflex in male rat offspring

• Published in: The Journal of nutrition Vol. 145; no. 5; pp. 907 - 914
• Main Authors: de Brito Alves, José L, Nogueira, Viviane O, Cavalcanti Neto, Marinaldo P, Leopoldino, Andréia M, Curti, Carlos, Colombari, Débora S A, Colombari, Eduardo, Wanderley, Almir G, Leandro, Carol G, Zoccal, Daniel B, Costa-Silva, João H
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2015
• Subjects: Animals; Birth Weight; Carotid Artery, Common - metabolism; Carotid Artery, Common - pathology; Carotid Artery, Common - physiopathology; Chemoreceptor Cells - metabolism; Chemoreceptor Cells - pathology; Diet, Protein-Restricted - adverse effects; Female; Fetal Development; Fetal Growth Retardation - etiology; Fetal Growth Retardation - physiopathology; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Lactation; Male; Maternal Nutritional Physiological Phenomena; Peripheral Nervous System - pathology; Peripheral Nervous System - physiopathology; Phrenic Nerve - pathology; Phrenic Nerve - physiopathology; Pregnancy; Prehypertension - etiology; Prehypertension - metabolism; Prehypertension - pathology; Prehypertension - physiopathology; Rats, Wistar; Respiratory System - pathology; Respiratory System - physiopathology; Sympathetic Nervous System - pathology; Sympathetic Nervous System - physiopathology; Thoracic Nerves - pathology; Thoracic Nerves - physiopathology; protein undernutrition; sympathetic overactivity; hypoxia-inducible factor 1 α; hypertension; peripheral chemoreflex
• ISSN: 0022-3166; 1541-6100
• DOI: 10.3945/jn.114.202804

Maternal protein restriction in rats increases the risk of adult offspring arterial hypertension through unknown mechanisms. 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. 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. 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. 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.