Cooperation between insulin and leptin in the modulation of vascular tone.
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.
Vecchione
Carmine
C
Department of Angio-Cardio-Neurology, La Sapienza University, Rome, Italy.
Aretini
Alessandra
A
Maffei
Angelo
A
Marino
Gennaro
G
Selvetella
Giulio
G
Poulet
Roberta
R
Trimarco
Valentina
V
Frati
Giacomo
G
Lembo
Giuseppe
G
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D046508:Culture Techniques; D004357:Drug Synergism; D019793:Fluorescein; D005456:Fluorescent Dyes; D007328:Insulin / Q000494:pharmacology*; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
C111205:4,5-diaminofluorescein; D005456:Fluorescent Dyes; D007328:Insulin; D020738:Leptin; D011518:Proto-Oncogene Proteins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019793:Fluorescein