Estradiol increases proteinuria and angiotensin II type 1 receptor in kidneys of rats receiving L-NAME and angiotensin II.
Prospective, placebo-controlled clinical trials suggest that estrogen may have adverse effects on the vascular system in women. The goal of this study was to determine if 17beta-estradiol (E2) would have adverse effects on the renovasculature in a rat model of renal injury characterized by low nitric oxide (NO) and high angiotensin II (AngII). We studied female Wistar rats that were sham-operated (sham), ovariectomized (OVX), or ovariectomized and replaced with E2 (OVX/E2). All rats were maintained on a high salt diet and renovascular injury was caused by treating rats with an inhibitor of NO synthase, N(omega)-nitro-L-arginine-methyl-ester (L-NAME), for 14 days, plus AngII on days 11 through 14. L-NAME/AngII treatment, as compared to placebo, caused proteinuria, glomerular injury, and fibrinoid necrosis of renal arterioles in sham-operated rats. Ovariectomy reduced L-NAME/AngII-induced renal damage, whereas E2 treatment increased L-NAME/AngII-induced damage in OVX rats. In rats treated with L-NAME/AngII, levels of AngII type 1 receptor (AT(1)R) protein were higher in the renal cortex of sham and OVX/E2 rats than in OVX rats. AT(1)R protein correlated with renal injury. E2 treatment also increased expression of AT(1)R mRNA. Thus, under conditions of low NO and high AngII, E2 exacerbated renal injury. E2-mediated increases in renal cortical AT(1)R expression may represent a novel mechanism for the adverse renovascular effects of estrogen.
Oestreicher
E M
EM
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Guo
C
C
Seely
E W
EW
Kikuchi
T
T
Martinez-Vasquez
D
D
Jonasson
L
L
Yao
T
T
Burr
D
D
Mayoral
S
S
Roubsanthisuk
W
W
Ricchiuti
V
V
Adler
G K
GK
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000009:adverse effects*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism; D010052:Ovariectomy; D011507:Proteinuria / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D004958:Estradiol; D019331:NG-Nitroarginine Methyl Ester