Published Online
on April 26, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on January 26, 2004
Revised on February 17, 2004

Reduced Uteroplacental Blood Flow Alters Renal Arterial Reactivity and Glomerular Properties in the Rat Offspring

Marijke W. Sanders; Gregorio E. Fazzi; Ger M.J. Janssen; Peter W. de Leeuw; Carlos E. Blanco; and Jo G.R. De Mey^*

From the Department of Pharmacology and Toxicology (M.W.S., G.E.F., G.M.J.J., J.G.R.D.M.), Cardiovascular Research Institute Maastricht (CARIM), University of Maastricht; Department of Internal Medicine (P.W.d.L.), University Hospital Maastricht; Department of Pediatrics (C.E.B.), Research Institute Growth and Development (GROW), University of Maastricht, the Netherlands.

^* To whom correspondence should be addressed. E-mail: J.DeMey{at}farmaco.unimaas.nl.

Abstract--Fetal malnutrition and hypoxia may modify organ system maturation and result in cardiovascular diseases in the adult. We tested whether intrauterine stress (IUS) leads to persistent alterations of renal biology. In rats, intrauterine stress was induced by ligation of the uterine arteries at day 17 of pregnancy. Renal arteries of the 21-day-old male offspring were isolated to study pharmacological reactivity. Kidneys were dissected to analyze renal structure and -adrenoceptor expression. At 21 days of age, half of the animals underwent unilateral left nephrectomy. At the age of 12 weeks, rats were instrumented for blood pressure monitoring, blood sampling, and renal function measurements. After IUS, litter size and birth weight were reduced, whereas the hematocrit was increased. Renal arterial responses to -adrenergic stimulation and sensitivity to adenylyl cyclase activation were increased, along with the renal expression of ₂-adrenoceptors. At 21 days and at 6 months of age, the number and density of the glomeruli were reduced, whereas their size was increased. The filtration fraction and urinary albumin concentration were increased 12 weeks after intrauterine stress. In control rats, removal of the left kidney at 21 days of age did not affect kidney function and blood pressure. However, after IUS, the remaining right kidney failed to compensate for the loss of the left kidney, and blood pressure was increased. In conclusion, prenatal stress transiently modifies renal arterial reactivity and results in long-lasting adverse effects on renal structure and function and on renal compensatory mechanisms.

Key words: hypertension • kidney • glomerular filtration rate • nephrectomy • pregnancy • rats • renal artery • receptors, adrenergic beta

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