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Effect of nitrendipine in a rat model of ischemic acute renal failure
Abstract:
An increase in intracellular calcium has been identified as an etiologic factor in acute renal failure (ARF) and blockade of slow calcium channels has been successful in its amelioration. Diuretics may also prevent or mitigate the effects of renal ischemia. We examined the actions of a new calcium channel blocker, nitrendipine (NTR), given intravenously to rats prior to bilateral clamping of the renal pedicle for 45-60 min. Four groups of rats were studied. Group I: Rats given the vehicle only and subjected to sham surgery had a creatinine clearance (Ccr) of .93 +/- .05 ml/min (n = 20). Group II: Rats given NTR (1 or 3 mg/kg) and subjected to sham surgery had a Ccr of .65 +/- .03 ml/min (n = 17). Group III: The infusion of the vehicle alone 10-15 min before clamping resulted in a Ccr of .12 +/- .02 ml/min (n = 23, p less than .001 vs. group I). Group IV: Rats given NTR and then clamped had a Ccr of .30 +/- .04 ml/min (n = 31, p less than .001 vs. group III, p less than .001 vs. group II). Higher doses of NTR did not improve the results. We concluded that NTR partially protects against ARF, but NTR lowered Ccr compared to control rats (p less than .001, group I vs. group II).
Insights
Nitrendipine (NTR) offers partial protection against acute renal failure (ARF) in rats by blocking calcium channels. However, NTR alone reduced kidney function compared to controls, indicating a complex effect on renal hemodynamics.
Area of Science:
- Nephrology
- Pharmacology
- Renal Physiology
Background:
- Increased intracellular calcium is implicated in acute renal failure (ARF).
- Calcium channel blockers and diuretics show potential in mitigating renal ischemia.
Purpose of the Study:
- To investigate the protective effects of nitrendipine (NTR), a novel calcium channel blocker, against ARF induced by renal pedicle clamping in rats.
Main Methods:
- Rats received intravenous nitrendipine (NTR) or vehicle prior to 45-60 minutes of bilateral renal pedicle clamping.
- Creatinine clearance (Ccr) was measured to assess renal function across four experimental groups.
Main Results:
- Vehicle-treated rats subjected to clamping showed significantly reduced Ccr (0.12 +/- 0.02 ml/min) compared to sham-operated controls (0.93 +/- 0.05 ml/min).
- NTR administration prior to clamping partially preserved Ccr (0.30 +/- 0.04 ml/min) compared to vehicle-treated clamped rats (p < .001).
- NTR alone, without clamping, decreased Ccr compared to controls (0.65 +/- 0.03 ml/min vs. 0.93 +/- 0.05 ml/min, p < .001).
Conclusions:
- Nitrendipine demonstrates partial protective efficacy against ischemic acute renal failure in rats.
- NTR administration alone negatively impacts renal function, suggesting a biphasic or dose-dependent effect requiring further investigation.