[Effects of leptin on RAAS and nitric oxide production in isolated rat glomeruli].

ABSTRACT

OBJECTIVE: To investigate the changes in angiotensinogen (AGT), angiotensin II type 1 receptor (AT(1)R), endothelial nitric oxide synthase (eNOS) mRNA and protein expressions and nitric oxide (NO) content in the rat glomeruli in response to leptin stimulation. METHODS: The glomeruli isolated from male SD rats were stimulated with 3 nmol/L leptin for 2 h. Real-time PCR and Western blotting were performed to analyze the mRNA and protein expressions of AGT, AT(1)R and eNOS in the glomeruli, and nitrite concentration in the glomeruli was measured by nitrate reductase assay. RESULTS: In comparison with the control group, exposure to leptin increased the mRNA levels of AGT, ATR(1) and eNOS in the isolated glomeruli by 2.69-/+0.17, 3.77-/+0.16 and 2.56-/+0.29 folds (P=0.024, 0.018 and 0.044), and their protein levels by 2.06-/+0.10, 2.67-/+0.08 and 1.61-/+0.13 folds (P=0.021, 0.015 and 0.032), respectively. The NO production in the glomeruli was also increased by 2.77-/+0.14 folds (P=0.000) following leptin exposure. CONCLUSION: Leptin exposure of isolated rat glomeruli directly causes activation of the internal renal renin-angiotensin system and enhanced NO production, suggesting that leptin plays a role in the pathogenesis of maladaptation in renal hemodynamics in obesity.