Chronic indomethacin administration and its relation with the renal kallikrein kinin system during rat pregnancy

The main purpose of the present study was to elucidate the potential role of vasodilator prostaglandins and the kallikrein kinin system in renal hemodynamic changes observed during rat gestation. Nineteen pregnant rats, un-treated and treated with Indomethacin (3 mg/kg body/wt) for 4 days during peak glomerular hyperfiltration, were studied before and during pregnancy. Twenty-two non-pregnant rats were also included as controls. Daily urinary volume, electrolytes and kallikrein excretion and creatinine clearance were measured along the experiment. Baseline creatinine clearance increased by 43% at the beginning of the third week of pregnancy to decline thereafter. Urinary kallikrein rose earlier, at the second week of pregnancy, and decreased near term while at the same time sodium excretion dropped by 30%. Indomethacin treatment prevented both the maximum increment in glomerular filtration rate occurring in normal pregnancy between days 14 to 18 and the physiological near term decline in kallikrein excretion. Furthermore, it induced an increase in sodium excretion in late pregnancy. These results suggest that vasodilator prostaglandins and the kallikrein kinin system may well participate in gestational hyperfiltration and sodium homeostasis of pregnant rats.