Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat.

Abstract

Micropuncture and morphologic studies were performed in six groups of male Munich-Wistar rats after removal of the right kidney and segmental infarction of two-thirds of the left kidney.Groups I and 4 received no specific therapy.Groups 2 and 5 were treated with the angiotensin I-converting enzyme inhibitor, enalapril, 50 mg/liter, in the drinking water.Groups 3 and 6 were treated with reserpine (5 mg/liter), hydralazine (80 mg/ liter), and hydrochlorothiazide (25 mg/liter).All rats were fed standard chow.Groups 1-3 underwent micropuncture study 4 wk after renal ablation.Untreated group 1 rats exhibited systemic hypertension and elevation of the single nephron glomerular fil- tration rate (SNGFR) due to high average values for the mean glomerular transcapillary hydraulic pressure gradient (AP) and glomerular plasma flow rate (QAJ.In group 2 rats, treatment with enalapril prevented systemic hypertension and maintained AP at near-normal levels without significant reduction in SNGFR and QA.In contrast, triple drug therapy normalized systemic hypertension, but failed to lower AP in group 3 rats.Groups 4- 6 were followed for 12 wk after renal ablation.Untreated group 4 rats demonstrated continuous systemic hypertension, progressive proteinuria, and glomerular structural lesions, including mesangial expansion and frequent areas of segmental sclerosis.In group 5 rats, treatment with enalapril maintained systemic blood pressure at normal levels over the 12-wk period and dra- matically limited the development of proteinuria and glomerular lesions.Despite equivalent systemic blood pressure control in group 6 rats, failure of triple drug therapy to control glomerular hypertension was associated with progressive proteinuria and glomerular lesions comparable to those seen in untreated group 4 rats.Thus, unless glomerular capillary hypertension is corrected, control of systemic blood pressure is insufficient to prevent progressive renal injury in rats with reduced renal mass. 1. Abbreviations used in this paper.Al, angiotensin I; AP, mean arterial pressure under anesthesia; GFR, glomerular filtration rate; Hct, hema- tocrit; Kf, glomerular capillary ultrafiltration coefficient; AP, mean glomerular transcapillary hydraulic pressure difference; PGC, mean glo- merular capillary hydraulic pressure; QA, glomerular capillary plasma flow rate; SN, single nephron; SNGFR, single nephron glomerular fil- tration rate.Hypertension and Glomerular Injury in Rats 1993