Role of Kinins in the Renoprotective Effect of Angiotensin–Converting Enzyme Inhibitors in Experimental Chronic Renal Failure

Abstract

The aim of this study was to investigate whether the renoprotective effect of angiotensin–converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Three groups of rats with 5/6 renal mass reduction were studied during the 14 weeks following surgery. One group received no therapy (control); the second group was treated from the beginning with the ACEI ramipril (1 mg/kg/day) added to the drinking water, and the last group received ramipril plus a β₂–bradykinin antagonist, HOE 140 (500 μg/kg/day) via osmotic minipumps. Plasma creatinine did not change in any group during the study. Urinary protein excretion rose in the controls from 9.18±1.6 to 45.0±5.6 mg/24 h at the end of the study. In ramipril group proteinuria was prevented (initial 7.5±1.0 and final 8.6±0.8 mg/24h). The effect of ramipril was abolished by HOE 140 (initial 11.6±2.0 and final 38.9±11 mg/ 24h). The systolic blood pressure of the controls increased from 106±2 to 144±5mmHg at the 14th week. Ramipril abolished the increase in systolic blood pressure. The effect of ramipril was reverted by HOE 140 (initial 108±2 and final 140±9 mmHg). Control rats had more severe histopathologic changes. Those animals receiving ramipril + HOE 140 displayed less severe glomerular changes, while rats treated only with ramipril had mild alterations. Thus the glomerular injury score was 2.11±0.32 for controls, 1.53±0.52 for rats treated with ramipril + HOE 140, and 0.06±0.04 for rats treated only with ramipril. The glomerular area was 20,886±1,410, 19,693±2,200 and 14,352±3,200 μm², respectively, for the 3 groups. These results suggest that the protective effect of ACEIs in the development of chronic renal failure is partially mediated by kinins.

Renoprotective Effects of Soy Protein Hydrolysates in N.OMEGA.-Nitro-L-Arginine Methyl Ester Hydrochloride-Induced Hypertensive Rats

“…Therefore, we used SPH to investigate its renoprotective effects in an L-NAME-induced hypertensive model, and we found a reduction in renal ACE activity and proteinuria in rats fed SPH, but no significant reduction in creatinine was found. Although Relative density captopril was shown to bring high creatinine levels back to normal (22), another ACE inhibitor, ramipril, decreased the blood pressure and prevented proteinuria without affecting plasma creatinine in rats with chronic renal failure (23). These inconsistent results suggest that different substances with ACE-inhibitory activities may exhibit different effects, and SPH in the present study may have been sufficient to partially correct renal alterations caused by an NO deficiency, but not to completely overcome all of them.…”

Effect of Mycophenolate Mofetil on Kallikrein Expression in the Kidney of 5/6 Nephrectomized Rats

“…A similar observation was reported by Shimamoto et al [20] who showed a reduction in the excretion of urinary kallikrein that correlated with an increase in blood pressure indicating that tubulointerstitial inflammation may be responsible for a deficient activity of the KKS and the development of hypertension. Further, kinins have been implicated in partially mediating the beneficial effects of angiotensin-converting enzyme inhibitors in rats with chronic renal failure [21] though experiments using the kinin B2 antagonist HOE140 have failed to prove it [22,23].…”

Differential Effects of Enalapril and Irbesartan in Experimental Papillary Necrosis

“…It is commonly accepted that with ACE inhibitors, the bradykinin lev-els increase, and the angiotensin II levels decrease, whereas with ARBs the bradykinin levels remain unchanged, and the angiotensin II levels actually increase. The role of bradykinin, however, remains controversial [24,25]. Conceivably, ARBs may be protective in hypertensive models, whereas ACE inhibitors may be preferred when the blood pressure is but mildly elevated.…”