Published Online
on June 30, 2003

A more recent version of this article appeared on August 1, 2003

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Submitted on April 7, 2003
Revised on April 24, 2003

Cooperation Between Insulin and Leptin in the Modulation of Vascular Tone

Carmine Vecchione; Alessandra Aretini; Angelo Maffei; Gennaro Marino; Giulio Selvetella; Roberta Poulet; Valentina Trimarco; Giacomo Frati; and Giuseppe Lembo^*

From the Department of Angio-Cardio-Neurology (C.V., A.A., A.M., G.M., G.S., R.P., V.T., G.F., G.L.), IRCCS Neuromed, Pozzilli (IS), and the Department of Experimental Medicine and Pathology (G.L.), La Sapienza University, Rome, Italy.

^* To whom correspondence should be addressed. E-mail: lembo{at}neuromed.it.

Abstract--High levels of insulin and leptin have been reported in human hypertension, suggesting a role for these metabolic hormones in blood pressure homeostasis. These hormones interact on intermediate metabolism, but nothing is known about their interaction at the vascular level. Our data demonstrate that insulin (0.6 nmol/L) is able to enhance vasodilation induced by leptin (10^-11 to 10^-6 mol/L; percentage change in maximal vasodilation, 39±3% vs 26±2%; n=6, P<0.03) but not by acetylcholine. Moreover, we demonstrate by 4,5-diaminofluorescein (DAF)-2 that insulin potentiates leptin-induced nitric oxide (NO) release. Finally, Western blotting studies show that insulin enhances the leptin-induced phosphorylation of Akt in Ser⁴⁷³ and Thr³⁰⁸ and of endothelial NO synthase in Ser¹¹⁷⁷. In conclusion, our data demonstrate that insulin and leptin cooperate in the modulation of vascular tone through enhancement of endothelial NO release. This phenomenon could have a major impact on the regulation of the cardiovascular system, principally in those clinical conditions characterized by endothelial NO dysfunction and metabolic disorders, such as arterial hypertension.

Key words: insulin • leptin • endothelium-derived factors • nitric oxide synthase • phosphorylation • vasorelaxation

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