Linked Life Data

15644487

Source:http://linkedlifedata.com/resource/pubmed/id/15644487

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-4-11
pubmed:abstractText
Impaired autoregulation in chronic kidney disease can result in elevation of glomerular capillary pressure and progressive glomerular damage; however, the factors linking chronic glomerular disorders to impaired autoregulation have not been identified. We tested the hypothesis that the cytokine most closely associated with progressive glomerular disease, transforming growth factor (TGF)-beta, may also attenuate autoregulation. Kidneys from normal rats were prepared for videomicroscopy, using the blood-perfused juxtamedullary nephron technique. Autoregulatory responses were measured under control conditions and during superfusion with TGF-beta1 (10 ng/ml). Control afferent arteriolar diameter averaged 18.4 +/- 1 microm and significantly decreased to 16.3 +/- 0.9 and 13.2 +/- 0.8 microm at perfusion pressures of 130 and 160 mmHg, respectively. In the presence of TGF-beta1, autoregulatory responses were completely blocked. In similar experiments performed using PDGF-BB (10 ng/ml) and HGF (25 ng/ml), the normal autoregulatory response was not affected. In vitro studies, using isolated preglomerular vascular smooth muscle cells, revealed that exposure to TGF-beta1 stimulated a rapid increase in reactive oxygen species (ROS) that was inhibited by NADPH oxidase inhibitors. In situ studies, with dihydroethidium staining, revealed a marked increase in renal vessel ROS production on exposure to TGF-beta1. Pretreatment of the juxtamedullary afferent arterioles with tempol, a ROS scavenger, or with apocynin, a NADPH oxidase inhibitor, prevented the impaired autoregulation induced by TGF-beta1. These data reveal a novel hemodynamic pathway by which TGF-beta could lead to progressive glomerular injury by impairing normal renal microvascular function.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
288
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F1069-77
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
TGF-beta impairs renal autoregulation via generation of ROS.
pubmed:affiliation
Dorrance Hamilton Research Laboratories, Division of Nephrology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA. Kumar.Sharma@jefferson.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't