Leptin inhibits angiotensin II-induced intracellular calcium increase and vasoconstriction in the rat aorta.
Besides its role in body weight control leptin may also act as a vasoactive hormone. This study was designed to investigate whether leptin modifies angiotensin II (ANG II)-induced vascular responses. The expression of functional leptin receptors (OB-Rb) was detected in vascular smooth muscle cells (VSMCs) from adult Wistar rats by RT-PCR. Immunocytochemistry and Western blot analysis further showed the expression of OB-R protein in VSMCs. The ANG II (10(-7) mol/liter)-induced increase in intracellular Ca(2+) was blocked (P < 0.01) by leptin (10(-8) mol/liter). Moreover, in calcium-free buffer leptin was able to inhibit 65% of the ANG II-induced calcium release from intracellular stores. In endothelium-denuded aortic rings from adult Wistar rats no effect of leptin on basal tension was observed. However, the ANG II-induced isometric contraction was reduced (P < 0.05) by leptin (10(-8) mol/liter). The experiments were also performed in age- and sex-matched Zucker rats, in which no effect of leptin on ANG II-induced calcium increase and vasoconstriction was observed. It is concluded that leptin blocks the vasoconstrictor action of ANG II and inhibits the ANG II-induced increase in intracellular Ca(2+) in VSMCs through OB-Rb. These findings provide new insight into the physiological effects of leptin on blood pressure regulation.
Division of Cardiovascular Pathophysiology, University of Navarra School of Medicine, Pamplona, Spain.
Ana
A
Fortuño
Amaia
A
Rodríguez
Javier
J
Gómez-Ambrosi
Paula
P
Muñiz
Javier
J
Salvador
Javier
J
Díez
Gema
G
Frühbeck
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D004730:Endothelium, Vascular / Q000502:physiology; D015870:Gene Expression; D007150:Immunohistochemistry; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D011924:Rats, Zucker; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000187:drug effects*
D002352:Carrier Proteins; D020738:Leptin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D000804:Angiotensin II; D002118:Calcium