Involvement of angiotensin II in glomerulosclerosis of stroke-prone spontaneously hypertensive rats.
Renal plasma flow (RPF), glomerular filtration rate (GFR), glomerular pathology and glomerular TGF-beta gene expression were examined in 12- and 24-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY). These parameters were also examined in SHRSP treated with equihypotensive doses of angiotensin II receptor antagonist (CV-11974:CV) and hydralazine (Hyd) for 12 weeks. Twelve-week-old SHRSP showed a decrease in RPF and GFR, and an increase in filtration fraction (FF) and urinary protein excretion (UP) compared to WKY. CV normalized these parameters, whereas although Hyd showed improved levels they were not to the levels achieved by the WKY. Glomerular TGF-beta expression was increased 2.0-fold in 12- and 24-week-old SHRSP, and CV, but not Hyd, decreased it to the control levels of WKY. At 24 weeks old, SHRSP showed a higher glomerulosclerosis index (GI) than WKY. CV, but not Hyd, lowered the GI to the level of the WKY controls. These data indicate that renal hemodynamic changes are closely associated with an increased TGF-beta expression in SHRSP and that this condition is caused by angiotensin II.
Nakamura
T
T
Department of Internal Medicine, Yamanashi Medical College, Japan.
Obata
J
J
Kuroyanagi
R
R
Kimura
H
H
Ikeda
Y
Y
Takano
H
H
Naito
A
A
Sato
T
T
Yoshida
Y
Y
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D015152:Blotting, Northern; D002561:Cerebrovascular Disorders / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D005923:Glomerulosclerosis, Focal Segmental / Q000209:etiology / Q000503:physiopathology*; D006973:Hypertension / Q000150:complications / Q000235:genetics / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects
D000804:Angiotensin II; D012313:RNA