Association between increased atrial natriuretic peptide and reduced cisplatin nephrotoxicity in rats.
Plasma atrial natriuretic peptide (ANP) concentrations were monitored in two experimental models of protection from cisplatin nephrotoxicity. Sprague-Dawley rats made diabetic with streptozotocin (65 mg/kg) were protected from cisplatin-induced nephrotoxicity when compared to control rats as indicated by reduced plasma creatinine (0.49 +/- 0.02 vs. 0.9 +/- 0.06 mg/dl; P less than .001) and blood urea nitrogen concentrations (18.51 +/- 1.4 vs. 43.08 +/- 2.1 mg/dl; P less than .001). Plasma ANP was also increased with experimental diabetes (76.5 +/- 8.98 fmol/ml) vs. normoglycemic controls (43.8 +/- 8.9 fmol/ml; P less than .02). When diabetic rats were treated with insulin, the renal protection observed with the diabetic state was reversed (creatinine, 0.70 +/- .05 mg/dl); plasma ANP concentrations were also reduced (52.2 +/- 15.2 fmol/ml). Renal platinum concentrations were significantly lower in the diabetic group and the reversal of diabetic-induced renal protection with insulin was associated with increased renal platinum concentrations. In rats given a single i.p. dose of cisplatin (5 mg/kg), a reduction in cisplatin-induced nephrotoxicity was observed when 5% NaCl was the vehicle of choice compared to that seen in rats given the same dose of drug in 0.9% saline (creatinine, 0.43 +/- 0.07 with 5% NaCl vs. 0.63 +/- 0.03 with 0.09% NaCl). NaCl (5%) administration also resulted in increased plasma ANP concentrations when compared to rats receiving equivalent volumes of 0.9% NaCl (88.4 +/- 6.2 vs. 50.5 +/- 5.6 fmol/ml, respectively). These data suggest that increased endogenous ANP may be a mechanism of renal protection common to both experimental diabetes and hypertonic saline administration. Chronically increased ANP may prevent renal accumulation of platinum in the kidney.
Ormond
P M
PM
Department of Pharmacology, Vanderbilt University, Nashville, Tennessee.
Basinger
M A
MA
Jones
M M
MM
Hande
K R
KR
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001786:Blood Glucose; D002945:Cisplatin / Q000633:toxicity*; D003404:Creatinine / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism*; D007328:Insulin / Q000008:administration & dosage; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010984:Platinum / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D007328:Insulin; D010984:Platinum; D009320:Atrial Natriuretic Factor; D003404:Creatinine; D002945:Cisplatin