Involvement of Nitric Oxide in Endothelium-Dependent Arterial Relaxation by Leptin

Leptin is a polypeptide, mainly produced in white adipose tissue, and increases sympathetic nerve activity. A few studies investigated leptin's effect on peripheral vessels. We examined the vasorelaxant effects of human leptin on rat arteries. Arterial rings were precontracted with 1 × 10−6 mol/l of phenylephrine, and leptin was superfused. Leptin relaxed phenylephrine-precontracted arterial rings in a dose-dependent manner. ED50 was calculated to 8.4 μg/ml. Removal of endothelium abolished the effects of leptin. Indomethacin (1 × 10−5 mol/l) did not affect the vasorelaxation by leptin, whereas 1 × 10−4 mol/l of Nω-nitro-L-arginine methyl ester (L-NAME) completely suppressed it. The inhibition was antagonized by 1 × 10−4 mol/l of L-arginine. Leptin normally relaxed arterial rings during superfusion of K channel blockers, including 3 × 10−5 mol/l of glibenclamide, 1 × 10−6 of mol/l apamin, and 5 × 10−7 mol/l of charybdotoxin. Low Cl− solution (8.3 mmol/l) inhibited leptin-induced relaxation, but endothelium-independent vasodilatation by nitroprusside was not impaired at low Cl− solution. These results suggest that arterial relaxation by leptin is mediated by nitric oxide released from endothelium, and Cl− plays an important role in leptin-induced nitric oxide release.