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Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate–salt hypertension
Author(s) -
Hisamichi Mikako,
KamijoIkemori Atsuko,
Sugaya Takeshi,
Ichikawa Daisuke,
Natsuki Takayuki,
Hoshino Seiko,
Kimura Kenjiro,
Shibagaki Yugo
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201600684rr
Subject(s) - endocrinology , medicine , renal injury , angiotensin ii , receptor , renin–angiotensin system , chemistry , kidney , blood pressure
The aim of this studywas 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. Transgenicmice 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 usedwith urinary L‐FABP as an indicator of tubulointerstitial damage. Those female mice were administered subcutaneously deoxycorticosterone acetate (DOCA)–salt tabletsplusdrinking water that contained1%saline for 28d after uninephrectomy. InL‐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, hypertensionwas similarly induced and the degree of glomerular damage was significantly more severe than in L‐FABP +/− AT1a +/+ ‐DOCAmice. Urinary L‐FABP levelswere significantly higher inL‐FABP +/− AT1a −/− ‐DOCAmice comparedwiththose in L‐FABP +/− AT1a +/+ ‐DOCAmice. 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. FASEB J. 31, 72–84 (2017) www.fasebj.org