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Renal Neuronal Nitric Oxide Synthase mRNA Expression is Enhanced by Hyperglycemia, but not by High Tubular Glucose

高血糖能增加腎臟神經性一氧化氮合成脢mRNA表現而腎小管高葡萄糖不能

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Increased neuronal NOS (nNOS) mRNA expression was found in the renal medulla of diabetic rats (Shih et al, Diabetologia 43: 649-659,2000). To furher investigate either hyperglycemia or high renal tubular glucose level enhanced renal nNOS synthesis, we measured nNOS mRNA in phlorizin-treated rat kidney. Male Wistar rats were divided into: (1) control (C,n=5); (2) phlorizin-treated control (C-P,n=5); (3)steptozotocin-induced diabetic rats (DM, n=6); (4) phlorizin-treated diabetic rats (DM-P,n=5). Phlorizin (40 mg/kg) was intraperitoneally administrated for 12 days after diabetic induction for 16 days. The mean blood glucose level of C, C-P, DM and DM-P groups were 119 ±4.9, 114±3.8, 438±15 and 202±12mg/dl, respectively. Daily urinary glucose excretion were 0.009±0.001, 3.0±0.13, 11.7±2.3 and 8.8±2.2 g/day. The relative nNOS/ß-actin mRNA ration in renal outer and inner medulla of DM 92.40±0.21 and 1.40±0.15)significantly increased as compared to C (1.00±0.28 and 1.00±0.18) and C-P (0.38±0.09 and 0.75 ±0.12). The relative nNOS/ß-actin mRNA ratios of outer and inner medulla in DM-P (1.50±0.34 and 0.88±0.06)are significantly decreased as compared to DM group. The nNOS-ß-actin mRNAratios of outer and inner medulla are significantly correlated with blood glucose level (r=0.696 and r=0.445), but not with urinary glucose excretion rate (r=0.378 and r=0.210)in four groups. Our results indicate that increased renal nNOS mRNA expression may directly be regulated by hyperglycemia, but not by high renal tubular glucose level in diabetic rat kidneys.

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