Mineralocorticoid receptor blockade and calcium

                Mineralocorticoid
receptor blockade and calcium channel blockade have different renoprotective
effects on glomerular and interstitial injury in rats.

We hypothesized that combination
treatment with the mineralocorticoid receptor antagonist
eplerenone and the calcium channel blocker amlodipine elicits better天津医科大学肿瘤医院泌尿肿瘤科杜君
renoprotective effects than monotherapy with either drug, via different
mechanisms in Dahl salt-sensitive (DS) hypertensive rats. DS rats
were fed a high-salt diet (4% NaCl) for 10 wk and were treated with
vehicle (n  12), eplerenone (50 mgkg1 day1, po, n  12),
amlodipine (3 mgkg1 day1, po, n  12), or eplerenone plus
amlodipine (n  12) after 2 wk of salt feeding. Vehicle-treated DS
rats developed proteinuria, which was attenuated by eplerenone or
amlodipine. Interestingly, eplerenone attenuated the glomerulosclerosis
and podocyte injury, but amlodipine did not. Conversely, treatment
with amlodipine markedly improved interstitial fibrosis, while the
effect of eplerenone was minimal. Combination treatment markedly
improved proteinuria, glomerulosclerosis, podocyte injury, and interstitial
fibrosis in DS rats. Renal hypoxia estimated by pimonidazole,
vascular endothelial growth factor expression, and density of peritubular
endothelial cells was exacerbated by salt feeding. Amlodipine,
either as monotherapy or in combination, ameliorated the renal hypoxia,
whereas eplerenone treatment had no effect. In conclusion, both
eplerenone and amlodipine attenuated renal injuries in high salt-fed
DS rats, but the targets for renoprotection differed between these two
drugs, with eplerenone predominantly acting on glomeruli and amlodipine
acting on interstitium. The combination of eplerenone and
amlodipine improved renal injury more effectively than either monotherapy
in high salt-fed DS rats, presumably by achieving their own
renoprotective effects.