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.

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The effect of verapamil, a Ca⁺⁺ antagonist drug, on renal function and proximal fluid reabsorption in normal and hypertensive (GΠ) rats was studied. During intravenous infusion of verapamil, mean arterial pressure (MAP) fell significantly in both groups, 23% more in hypertensive than in normotensive rats. Glomerular filtration rate (GFR) was significantly higher in hypertensive rats and also increased significantly in this group during verapamil infusion. Effective renal plasma flow (ERPF) was similar in both groups and did not change significantly during verapamil infusion. The increase in urine flow, Na⁺ and Ca⁺⁺ excretion was higher in hypertensive than in normotensive rats during verapamil infusion. When 10^-5M verapamil was added to the luminal perfusate of proximal tubules, fluid reabsorption was reduced to 64% in normotensive and to 42% in hypertensive rats. When added to capillary perfusate, fluid reabsorption was almost completely but reversibly inhibited (92% in normotensive and 83% in hypertensive rats). Our findings indicate a direct effect of verapamil on renal Na⁺ and possibly also on Ca⁺⁺ reabsorption, suggesting involvement of the Na⁺-Ca⁺⁺ countertransport system. The greater effect of verapamil on Na⁺ excretion in hypertensive rats was not due to increased action on proximal Na⁺ reabsorption.

Background/Aims: Reduction in renal mass by uninephrectomy induces a functional compensation in the remnant kidney. The activity of the angiotensin-converting enzyme (ACE) as well as renin mRNA in the proximal convoluted tubule (PCT) of uninephrectomized (UNx) rats increases. The aim of this work was to determine whether the increased activity of the local renin-angiotensin system (RAS) participates in the adaptation of renal function after uninephrectomy. Method: We utilized normal two-kidney (2K) and 3-week UNx rats to study the activity of the ACE in vesicles obtained from luminal membranes of proximal tubular cells and the acidification kinectics in PCTs using micropuncture techniques. Results: The converting enzyme activity was significantly larger in UNx (5.87 ± 0.69 nmol · min^–1 · mg protein^–1) than in 2K rats (2.43 ± 0.13 nmol · min^–1 · mg protein^–1; p < 0.05). The acidification rate constant (κ) in PCT of 2K rats was 0.18 ± 0.02 s^–1 and in UNx rats 0.30 ± 0.04 s^–1 (p < 0.001). In UNx rats, microperfusion with 10^–5 M ramipril or 10^–5 M losartan decreased κ to 0.19 ± 0.02 and 0.18 ± 0.02 s^–1, respectively, but had no effect on 2K rats. Luminal steady-state pH (pH_∞) was the same in 2K and UNx rats, and was not modified by addition of 10^–5 M ramipril or 10^–5 M losartan in both groups. The proximal H⁺ flux (J_H⁺), calculated from pH_∞ and κ, was 1.12 nmol · cm^–2 · s^–1 in 2K rats and, 1.77 nmol · cm^–2 · s^–1 in UNx rats (p < 0.001). In 2K rats, this value was not changed by 10^–5 M ramipril or 10^–5 M losartan, but in UNx rats J_H⁺ decreased 25 and 30% with ramipril or losartan, respectively (p < 0.001). Conclusions: These data suggest that the increase in the local RAS activity could be an adaptive change that contributes to maintain the homeostasis of body fluids after uninephrectomy.

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