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

J Nutr. 2015 May;145(5):907-14. doi: 10.3945/jn.114.202804. Epub 2015 Feb 18.

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.

Keywords: hypertension; hypoxia-inducible factor 1 α; peripheral chemoreflex; protein undernutrition; sympathetic overactivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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

Substances

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