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

Abstract

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.

• Authors: José L de Brito Alves, Viviane O Nogueira, Marinaldo P Cavalcanti Neto, Andréia M Leopoldino, Carlos Curti, Débora S A Colombari, Eduardo Colombari, Almir G Wanderley, Carol G Leandro, Daniel B Zoccal, João H Costa-Silva
• Journal: The Journal of nutrition (J Nutr) Vol. 145 Issue 5 Pg. 907-14 (May 2015) ISSN: 1541-6100 [Electronic] United States
• PMID: 25934662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Society for Nutrition.

Chemical References

• Hif1a protein, rat
• Hypoxia-Inducible Factor 1, alpha Subunit

Topics

• Animals
• Birth Weight
• Carotid Artery, Common (metabolism, pathology, physiopathology)
• Chemoreceptor Cells (metabolism, pathology)
• Diet, Protein-Restricted (adverse effects)
• Female
• Fetal Development
• Fetal Growth Retardation (etiology, physiopathology)
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Lactation
• Male
• Maternal Nutritional Physiological Phenomena
• Peripheral Nervous System (pathology, physiopathology)
• Phrenic Nerve (pathology, physiopathology)
• Pregnancy
• Prehypertension (etiology, metabolism, pathology, physiopathology)
• Rats, Wistar
• Respiratory System (pathology, physiopathology)
• Sympathetic Nervous System (pathology, physiopathology)
• Thoracic Nerves (pathology, physiopathology)