Role of angiotensin II type 1a receptor in renal injury induced by deoxycorticosterone acetate-salt hypertension.

ABSTRACT: 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.

SUBMITTER: Hisamichi M 

PROVIDER: S-EPMC5161521 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature