Effect of chronic therapy with proteolytic enzymes on hypertension-inducedrenal injury in the rat model of Goldblatt hypertension

This study investigated the possible beneficial effect of intraperitoneal p roteolytic enzyme administration on the development of hypertension-induced renal injury in the rat model of 2-kidney 1-clip (2K1C) Goldblatt hyperten sion. Male Wistar rats (120-150 g) underwent either sham surgery (control, n = 5) or clipping of the left renal artery. From day one 2K1C rats were ra ndomized into 2 groups, placebo treatment (n = 7), and proteolytic enzyme t reatment (n = 9). To the verum group a fixed mixture of trypsin (2.42 mg), bromelain (4.54 mg), and rutin (5.04 mg) dissolved in 2 mi of sterile 0.9% NaCl was administered intraperitoneally daily, while the placebo group rece ived only vehicle. Rats were pair-fed. The duration of the study was 7 week s. All 2K1C rats developed hypertension and the mean values of systolic blo od pressure (SBP) did not differ significantly between the groups at any ti me recorded (SBP at sacrifice: controls 122.0 +/- 8.5 mm Hg; placebo 191.4 +/- 7.6 mm Hg; enzyme 180.5 +/- 6.5 mm Hg). Enzyme treatment prevented the rise in proteinuria (controls 12.4 +/- 2.6 mg/24 h; placebo 19.7 +/- 3.9 mg /24 h; enzyme 12.2 +/- 1.3 mg/24 h; p < 0.05) and ameliorated the increase in serum urea concentrations. Histomorphologically, signs of malignant neph rosclerosis were not found in control rats, while they were present in 4/7 (57%) of placebo-treated rats, but only in 1/9 (11%) of the enzyme-treated group. The volume fraction of renocortical interstitium was increased in bo th 2K1C groups in comparison with controls, however, enzyme treatment decre ased the accumulation of interstitial tissue significantly (-22%) compared to placebo treatment. Cellular infiltration with mononuclear cells was also lower in the protease-treated group. To summarize, in the rat model of 2K1 C hypertension, systemic treatment with proteases ameliorates the severity of nephrosclerosis and tubulointerstitial fibrosis in the non-clipped kidne y, as well as proteinuria, without affecting high blood pressure.