Cardiovascular and renal profiles in rat offspring that do not undergo catch-up growth after exposure to maternal protein restriction

Ryan J. Wood-Bradley, Sarah L. Henry, Roger G. Evans, John F. Bertram, Luise A. Cullen-McEwen, James A. Armitage

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Maternal protein restriction is often associated with structural and functional sequelae in offspring, particularly affecting growth and renal-cardiovascular function. However, there is little understanding as to whether hypertension and kidney disease occur because of a primary nephron deficit or whether controlling postnatal growth can result in normal renal-cardiovascular phenotypes. To investigate this, female Sprague-Dawley rats were fed either a low-protein (LP, 8.4% protein) or normal-protein (NP, 19.4% protein) diet prior to mating and until offspring were weaned at postnatal day (PN) 21. Offspring were then fed a non 'growth' (4.6% fat) which ensured that catch-up growth did not occur. Offspring growth was determined by weight and dual energy X-ray absorptiometry. Nephron number was determined at PN21 using the disector-fractionator method. Kidney function was measured at PN180 and PN360 using clearance methods. Blood pressure was measured at PN360 using radio-telemetry. Body weight was similar at PN1, but by PN21 LP offspring were 39% smaller than controls (Pdiet < 0.001). This difference was due to proportional changes in lean muscle, fat, and bone content. LP offspring remained smaller than NP offspring until PN360. In LP offspring, nephron number was 26% less in males and 17% less in females, than NP controls (Pdiet < 0.0004). Kidney function was similar across dietary groups and sexes at PN180 and PN360. Blood pressure was similar in LP and NP offspring at PN360. These findings suggest that remaining on a slow growth trajectory after exposure to a suboptimal intrauterine environment does not lead to the development of kidney dysfunction and hypertension.

Original languageEnglish
Pages (from-to)426-436
Number of pages11
JournalJournal of Developmental Origins of Health and Disease
Volume14
Issue number3
DOIs
Publication statusPublished - 1 Jun 2023

Keywords

  • blood pressure
  • Developmental programming
  • kidney function
  • low protein diet
  • maternal nutrition
  • nephron number
  • stereology
  • telemetry

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