Effect of diltiazem and methyldopa on gestation-related renal complications in rats with adriamycin nephrosis : relationship to glomerular prostanoid synthesis

In the presence of pre-existing renal disease, occurrence of hypertension during pregnancy may compromise renal function and aggravate proteinuria. In pregnant rats with early adriamycin nephropathy, this is associated with an increase in the glomerular TxB2:PGE2 ratio. In the present study we evaluated the effect of blood-pressure control on renal function and its relationship with glomerular prostanoid synthesis. Pregnant Wistar rats with adriamycin nephropathy received diltiazem, 30 mg/kg/day or methyldopa, 400 mg/kg/day from mid-gestation. Mean arterial pressure (MAP), inulin clearance (CIN), urine protein excretion (UP) and glomerular prostanoid synthesis were measured. Results were compared with (i) untreated pregnant rats with adriamycin nephropathy, (ii) virgin rats with adriamycin nephropathy, and (iii) normal virgin or (iv) pregnant normal rats. MAP increased in untreated pregnant rats with adriamycin nephropathy (P < 0.01 versus virgin rats with adriamycin nephropathy), contrasting with the physiological decrease observed in normal pregnant rats. Diltiazem and methyldopa decreased MAP to normal values. In untreated pregnant rats with adriamycin nephropathy CIN decreased and proteinuria increased significantly at the end of gestation. Treatment with diltiazem and methyldopa augmented GFR, but only diltiazem decreased UP significantly. It was associated with an increased glomerular PGE2 synthesis. We conclude that in rats with adriamycin nephropathy, antihypertensive treatment improved GFR. Diltiazem also decreased urinary protein excretion, associated with a normalization of the glomerular TxB2:PGE2 ratio.