This Article Full Text Full Text (PDF) All Versions of this Article: 48/4/717    most recent 01.HYP.0000237973.64711.e2v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bursztyn, M. Articles by Ariel, I. Search for Related Content PubMed PubMed Citation Articles by Bursztyn, M. Articles by Ariel, I. Related Collections Animal models of human disease Other hypertension

(Hypertension. 2006;48:717.)
© 2006 American Heart Association, Inc.

Original Articles

Adult Hypertension in Intrauterine Growth-Restricted Offspring of Hyperinsulinemic Rats

Evidence of Subtle Renal Damage

Michael Bursztyn; Marie-Luise Gross; Tania Goltser-Dubner; Nadja Koleganova; Tatiana Birman; Yoav Smith; Ilana Ariel

From the Departments of Medicine (M.B.), Pathology (T.B., I.A.), Psychiatry (T.G-D.), and Bioinformatics Center (Y.S.), Hadassah-Hebrew University Medical Center, Mount-Scopus, Jerusalem, Israel; Ein-Kerem (Y.S.), Jerusalem, Israel; and the Institute of Pathology (M-L.G., N.K.), Ruprecht-Karl University, Heidelberg, Germany.

Correspondence to Michael Bursztyn, Hypertension Unit, Department of Medicine, Hadassah-Hebrew University Medical Center, Mount Scopus, PO Box 24035, Jerusalem 91240, Israel. E-mail bursz{at}cc.huji.ac.il

In humans, intrauterine growth-restricted newborns are prone to develop hypertension as adults. We studied a rat model of pregnancy-induced hypertension associated with intrauterine growth restriction (IUGR) produced by chronic administration of insulin. Fetuses of hyperinsulinemic dams (HDs) were smaller than those of normal dams (5.1±0.4 g versus 5.6±0.1 g, respectively; P<0.05). At 16 weeks of age, tail-cuff systolic blood pressure was measured, the rats were placed in metabolic cages and euthanized, and the kidneys were examined. Male but not female offspring of HDs (n=9) had higher blood pressure than normal-pregnancy offspring (n=12; 148±11 mm Hg versus 118±14 mm Hg; P<0.004). In contrast to other models, there was no difference in ours in the number and volume of glomeruli. However, there were significantly greater glomerular, tubulointerstitial, and vascular damage indices in the kidneys of male HD offspring versus controls (2.01±0.34 versus 1.08±0.16, 1.80±0.34 versus 0.76±0.12, and 2.13±0.81 versus 0.78±0.16, respectively; P<0.0001), with similar tubulointerstitial findings in females. Increased expression of collagen type IV, a kidney damage marker indicating fibrosis, was found in the tubulointerstitium. This may be associated with downregulation of bone morphogenetic protein 6, a presumptive antifibrogenic agent, at the end of gestation. In conclusion, male offspring of HDs displayed IUGR and adult hypertension accompanied by several indices of renal fibrosing damage, mainly in the renal tubulointerstitium. Our findings suggest that there is >1 pathway of fetal programming leading from IUGR to development of hypertension in later life.

Key Words: gene expression • hypertension, experimental • insulin • renal disease • pregnancy