gms | German Medical Science

We tested the hypothesis that statins reduce glomerulosclerosis in a low-renin model of hypertension. Two weeks after uninephrectomy, male Sprague-Dawley rats received deoxycorticosterone-acetate (DOCA) pellets subcutaneously, or were sham operated. All animals received 1% NaCl for drinking. DOCA rats were treated with fluvastatin (5 mg/kg, daily gavage) or vehicle for 6 weeks. During treatment, 4 of 13 vehicle-treated DOCA hypertensive rats died whereas all 7 fluvastatin-treated DOCA rats, and all 12 normotensive controls, survived. At the end of treatment, mean blood pressure measured intraarterially in conscious rats was elevated in vehicle-treated DOCA rats (185±11 versus 111±3 mmHg in normotensive rats, p<0.001) and somewhat lower in fluvastatin-treated DOCA rats (156±7 mmHg, p=0.049 versus vehicle). Urinary protein excretion was grossly elevated in vehicle-treated DOCA rats (696±72 versus 34±4 mg/day/rat in normotensive controls) but markedly reduced by fluvastatin (365±94 mg/day/rat, p=0.003). DOCA rats developed marked glomerulosclerosis (index: 2.0±0.1 versus 0.5±0.1 in controls, p<0.001) which was alleviated by fluvastatin (1.5±0.2, p=0.021 versus vehicle). To test whether suppression of inflammatory changes mediates the effects of fluvastatin, we quantified macrophage infiltration after staining for ED-1. Glomerular infiltration of macrophages in DOCA rat kidneys (4.2±0.3 versus 0.9±0.1 macrophages per glomerular cross-section in normotensive controls, p<0.001) was markedly reduced by fluvastatin (2.4±0.6 macrophages per cross-section, p=0.005). We conclude that statins reduce the extent of hypertension, proteinuria and glomerulosclerosis in a low-renin model of severe hypertensive glomerular disease. Reduction of glomerular macrophage infiltration may contribute to the protective effect of statins in hypertensive glomerulosclerosis.