Herein, we studied the effects of the novel nonsteroidal selective
mineralocorticoid receptor (MR) blocker,
esaxerenone, on blood pressure and renal injury in Dahl
salt-sensitive (DSS) rats. We also monitored intact urinary and total
angiotensinogen (AGT). DSS rats were given a normal
salt diet (NS: 0.4% NaCl, n = 10), a high-
salt diet (HS: 8% NaCl, n = 10), HS + esaxerenone (1 mg/kg/day, p.o., n = 10), or HS + losartan (
angiotensin II receptor blocker, 10 mg/kg/day, p.o., n = 10) for 6 weeks. Glomerular and tubulointerstitial tissues were obtained via a
laser capture method. HS-treated DSS rats developed
hypertension,
albuminuria, and glomerular injury, which were associated with increased glomerular
desmin staining and reduced
mRNA levels of glomerular
podocin and
nephrin. HS-treated DSS rats also showed tubulointerstitial
fibrosis with an increase in renal oxidative stress (4-hydroxynonenal staining). The urinary ((total AGT-intact AGT)/intact AGT) ratio, an
indicator of intrarenal
renin activity, was significantly suppressed in HS-treated DSS rats. Treatment with
esaxerenone significantly decreased blood pressure, while
losartan did not. Furthermore,
esaxerenone attenuated the development of
albuminuria, glomerular injury, and tubulointerstitial
fibrosis more than
losartan did, and this effect was associated with reduced renal oxidative stress. These data indicate that
esaxerenone has
antihypertensive and renal protective effects in
salt-dependent hypertensive mice with suppressed intrarenal
renin activity, as indicated by low levels of the urinary (total AGT-intact AGT)/intact AGT ratio.