Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension.
The aim of this study was to investigate the in vivo role of angiotensin II type 1a (AT1a) receptor in renal damage as a result of hypertension by using transgenic mice with AT1a receptor gene disruption. Transgenic mice that express human liver-type fatty acid binding protein (L-FABP) with or without disruption of the AT1a receptor gene (L-FABP+/-AT1a-/-, and L-FABP+/-AT1a+/+, respectively) were used with urinary L-FABP as an indicator of tubulointerstitial damage. Those female mice were administered subcutaneously deoxycorticosterone acetate (DOCA)-salt tablets plus drinking water that contained 1% saline for 28 d after uninephrectomy. In L-FABP+/-AT1a+/+mice that received DOCA-salt treatment, hypertension was induced and slight expansion of glomerular area, glomerular sclerosis, and tubulointerstitial damage were observed. In L-FABP+/-AT1a-/-mice that received DOCA-salt treatment, hypertension was similarly induced and the degree of glomerular damage was significantly more severe than in L-FABP+/-AT1a+/+-DOCA mice. Urinary L-FABP levels were significantly higher in L-FABP+/-AT1a-/--DOCA mice compared with those in L-FABP+/-AT1a+/+-DOCA mice. Hydralazine treatment significantly attenuated renal damage that was found in L-FABP+/-AT1a-/--DOCA mice along with a reduction in blood pressure. In summary, activation of the AT1a receptor may contribute to maintenance of the glomerular structure against hypertensive renal damage.-Hisamichi, M., Kamijo-Ikemori, A., Sugaya, T., Ichikawa, D., Natsuki, T., Hoshino, S., Kimura, K., Shibagaki, Y. Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension.
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Mikako
M
Hisamichi
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan; a2kamijo@marianna-u.ac.jp.|Department of Anatomy, St. Marianna University School of Medicine, Kawasaki, Japan.
Atsuko
A
Kamijo-Ikemori
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Takeshi
T
Sugaya
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Daisuke
D
Ichikawa
Institute for Ultrastructural Morphology, St. Marianna University School of Medicine, Kawasaki, Japan.
Takayuki
T
Natsuki
Department of Anatomy, St. Marianna University School of Medicine, Kawasaki, Japan.
Seiko
S
Hoshino
Department of Internal Medicine, Japan Community Health Care Organization, Tokyo Takanawa Hospital, Tokyo, Japan.
Kenjiro
K
Kimura
Division of Nephrology and Hypertension, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Japan.
Yugo
Y
Shibagaki
D000818:Animals; D003900:Desoxycorticosterone / Q000633:toxicity*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000209:etiology / Q000473:pathology; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000473:pathology; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride / Q000633:toxicity*
C493319:FABP1 protein, human; D050556:Fatty Acid-Binding Proteins; D026561:Low Density Lipoprotein Receptor-Related Protein-2; C055127:Lrp2 protein, mouse; D044140:Receptor, Angiotensin, Type 1; D003900:Desoxycorticosterone; D012965:Sodium Chloride
Ang II AT1a receptor; DOCA; L-FABP; hypertension
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