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.