Dose Effect of Captopril on Renal Hemodynamics and Proteinuria in Conscious,Partially Nephrectomized Rats

Abstract

Abstract

The effect of varying doses of captopril, an angiotensin l-converting enzyme inhibitor, on renal hemodynamics, systemic arterial pressure, and the progression of chronic renal disease in conscious, three-quarter nephrectomized adult male Sprague-Dawley rats was studied. Six weeks following nephrectomy (Week 0), rats were randomly divided into five groups. Groups 2 (n = 8), 3 (n = 8), 4 (n = 9), and 5 (n = 5) were given 5, 10, 20, and 40 mg/kg captopril, respectively, daily in drinking water. Group 1 (n = 7) and sham-operated controls (n = 7) were given water only. On Weeks −6, 0, 2, and 4, renal function was assessed by 24-hr urinary protein excretion and plasma creatinine. Systolic blood pressure was measured at these times by the tail cuff method. Following Week 4, glomerular filtration rate and effective renal plasma flow were measured in conscious rats by single injection clearance of [³H]inulin and [¹⁴C]tetraethylammonium bromide, respectively. Group 1 had significantly higher (P < 0.05) 24-hr urinary protein excretion, plasma creatinine, and systolic pressure compared with Group 5 and controls by Week 4, whereas values for these parameters for Groups 2–4 ranged between these extremes. Although systolic pressures were not significantly different (P > 0.05), Group 2 had significantly lower proteinuria than Group 1 (P < 0.05) at Week 4. Total kidney glomerular filtration rate was similarly decreased in Groups 1–5 compared with control rats. Total kidney effective renal plasma flow was higher in captopril-treated groups than in Group 1, whereas systolic blood pressure was similar or lower, indicating that captopril reduced renal vascular resistance. Furthermore, unlike Groups 1–3, the groups receiving higher doses of captopril (4 and 5) did not develop anemia associated with chronic renal disease. In conclusion, captopril attenuated renal functional deterioration in a dose-related manner. The effect on proteinuria was evident at low doses of captopril which did not significantly reduce systemic blood pressure and was accompanied by an increase in effective renal plasma flow and a decrease in renal vascular resistance.