title: Renal injury from angiotensin II-mediated hypertension.
abstract: Angiotensin II (Ang II)-mediated hypertension induces vascular smooth muscle cell hypertrophy and hyperplasia in systemic blood vessels, but the effects of Ang II on the intrinsic cell populations within the kidney have been less well characterized. We infused Ang II for 14 days into rats by minipump at doses (200 ng/min) that resulted in moderate hypertension (mean systolic blood pressure 156-172 mm Hg). Small renal arterial vessels of Ang II-infused rats demonstrated focal injury with fibrinoid necrosis and medial hyperplasia, whereas the glomerular capillaries demonstrated only rare segmental hyalinosis. Proliferation of vascular smooth muscle cells was pronounced (fourfold to 20-fold increase in [3H]thymidine incorporation) as opposed to a minimal proliferation of glomerular cells in Ang II-infused rats. In contrast, the principal effect of Ang II in glomeruli was to increase the expression of alpha-smooth muscle actin by mesangial cells and desmin by visceral glomerular epithelial cells. Ang II-infused rats also developed focal tubulointerstitial injury, with tubular atrophy and dilation, cast formation, an interstitial monocytic infiltrate, and mild interstitial fibrosis with increased type IV collagen deposition. The injury was associated with a proliferation of distal tubule, collecting duct, and interstitial cells as determined by immunostaining for proliferating cell nuclear antigen, and was accompanied by an increase in platelet-derived growth factor B-chain messenger RNA in the area of interstitial injury as localized by in situ hybridization. Renal interstitial cells also underwent phenotypic modulation in which they expressed alpha-smooth muscle actin. Vehicle-infused control rats displayed no tubular injury, proliferation, or phenotypic modulation. Thus, Ang II in doses that cause moderate hypertension induces marked vascular, glomerular, and tubulointerstitial injury with cell proliferation, leukocyte recruitment, phenotypic modulation with the upregulation of proteins normally associated with smooth muscle cells, and interstitial fibrosis.
authors.affiliation: Department of Medicine, University of Washington, Seattle 98195.
authors.forename: R J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: C E
authors.initials: CE
authors.lastname: Alpers
authors.forename: A
authors.initials: A
authors.lastname: Yoshimura
authors.forename: D
authors.initials: D
authors.lastname: Lombardi
authors.forename: P
authors.initials: P
authors.lastname: Pritzl
authors.forename: J
authors.initials: J
authors.lastname: Floege
authors.forename: S M
authors.initials: SM
authors.lastname: Schwartz
mesh_terms: D000804:Angiotensin II / Q000008:administration & dosage / Q000502:physiology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D015918:Infusion Pumps, Implantable; D007668:Kidney / Q000473:pathology*; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology; D007684:Kidney Tubules / Q000473:pathology; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000187:drug effects
chemical_list: D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D000804:Angiotensin II; D012083:Renin