Reduced nephron number in adult sheep, hypertensive as a result of prenatal glucocorticoid treatment

J Physiol. 2003 Jun 15;549(Pt 3):929-35. doi: 10.1113/jphysiol.2003.042408. Epub 2003 May 2.

Abstract

There is some evidence, mainly from rodent studies, that any factor which alters the final total number of nephrons formed, during nephrogenesis, will result in hypertension in adult life. Sheep, programmed to become hypertensive by exposure to synthetic glucocorticoid (dexamethasone, 0.48 mg h-1, for 48 h) early in development (~27 days of gestation), were killed at 7 years of age, and had nephron counting performed by unbiased stereology. Mean arterial pressure was 83 +/- 4 mmHg in the dexamethasone (DEX) group (n = 5), and 73 +/- 5 in the control (CON; n = 7; P < 0.05). The total nephron number, in the right kidney (249 070 +/- 14 331; n = 5) was significantly lower (P < 0.01) than that of controls (402 787 +/- 30 458; n = 7). Mean glomerular volume was larger in the DEX than the CON group (P < 0.01), but there was no significant difference in the sclerosis index between the two groups. Low nephron number was associated with grossly enlarged and dilated proximal tubules and greater accumulation of collagen type I and type III in the tubular interstitium and periadventitia of the renal cortical vessels. These data suggest that the hypertensive programming effect of glucocorticoid treatment, early in kidney development, results, at least in part, from impaired nephrogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Animals
  • Body Weight / physiology
  • Collagen / metabolism
  • Dexamethasone / pharmacology
  • Female
  • Glomerulosclerosis, Focal Segmental / pathology
  • Glucocorticoids / pharmacology*
  • Hypertension / chemically induced
  • Hypertension / pathology*
  • Kidney / pathology
  • Kidney Glomerulus / pathology
  • Nephrons / pathology*
  • Organ Size / drug effects
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Sheep / physiology*

Substances

  • Glucocorticoids
  • Dexamethasone
  • Collagen