EFFECT OF L-ARGININE TREATMENT IN PREGNANT RATS WITH ADRIAMYCIN NEPHROPATHY

Objective: The influence of pregnancy (P) on the evolution of primary renal disease is still controversial. In rats with early adriamycin nephropathy (ADR), pregnancy enhanced mean arterial pressure (MAP) and urine protein excretion (UP). It has been suggested that the development of hypertension in pregnancy may be related to a decreased synthesis of vasodilatory substance(s) by endothelial cells. In the present study, the effect of L-arginine, a precursor of the endothelium-derived relaxing factor nitric oxide (NO), was evaluated. Methods: Four groups of rats were studied (n = 10 each): 1-normal pregnancy (NP); 2-normal pregnancy treated with L-arginine (NP+LA); 3-ADR pregnant rats (ADRP); and 4-ADR pregnant rats treated with L-arginine (ADRP + LA). L-arginine, 2 g/l, was added to the drinking water from midpregnancy. Results: In ADRP rats, MAP increased to 135 +/- 4.1 mm Hg, significantly above the values of 91 +/- 1.2 mm Hg found in NP rats, P < .01. Treatment with L-arginine did not influence MAP in NP+LA rats, whereas in ADRP+LA animals, MAP decreased to 89 +/- 5 mm Hg, P < .01 vs. ADRP. In ADRP rats, UP increased from 11 +/- 4 mg/d before P to 315 +/- 55 mg/d at end P. By contrast, in ADRP+LA rats, UP increased only to 98 +/- 23 mg/d, P < .01 vs. ADRP rats. Inulin clearance was significantly greater in ADRP+LA than in ADRP rats, 2.37 +/- .21 vs. 1.45 +/- .01 ml/min, respectively, P < .01. Conclusions: These preliminary results suggested that in rats with incipient adriamycin nephropathy, the endogenous synthesis of NO might be inadequately low during pregnancy, leading to the development of hypertension and enhancement of urine protein excretion.