Faculty Collaboration Database

Angiotensinogen modulates renal vasculature growth. Hypertension 2006 Jun;47(6):1067-74

Date

04/26/2006

Pubmed ID

16636191

DOI

10.1161/01.HYP.0000221065.05670.23

Scopus ID

2-s2.0-33745003459 (requires institutional sign-in at Scopus site)   14 Citations

Abstract

We have shown previously that angiotensinogen, like other members of the serine protease inhibitor family, has antiangiogenic properties in vitro on cultured endothelial cells and in ovo in the chick chorioallantoic membrane assay. The aim of this study was to show the effects of angiotensinogen on vascular wall remodeling in vivo. We measured the vessel wall thickness (tunica media) stained with an antibody to alpha-actin. In the kidney, arterioles were 21.5% thinner in male transgenic mice overexpressing human angiotensinogen than in male control animals. In other vascular beds, the arterial wall thickness was not affected. By using in situ hybridization and Northern blot analysis, human angiotensinogen expression was detected at a high level in the male kidney and at a much lower level in other organs. There is a relationship between the effect of angiotensinogen on arterial wall thickness and the local expression level of angiotensinogen in this model of transgenic mice. Because human angiotensinogen is not cleaved to a significant extent by mouse renin, the reduction in kidney arterial wall thickness is because of angiotensinogen itself and not angiotensin II, and we show that the reduction was not because of hypoplasia or hypotropia. In contrast, a marked difference in the expression of platelet-derived growth factor receptor-beta was observed in the kidney arterioles at day 5 when compared with controls. Altogether, these observations provide the first quantitative evidence that a high level of angiotensinogen expression can inhibit the growth of kidney artery walls in vivo.

Author List

Brand M, Lamandé N, Sigmund CD, Larger E, Corvol P, Gasc JM

Author

Curt Sigmund PhD Chair, Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Angiotensinogen
Animals
Apoptosis
Blood Vessels
Cell Count
Cell Proliferation
Female
Humans
Kidney
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
RNA, Messenger
Renal Artery
Tissue Distribution