Copyright © 2007, European Society of Cardiology
Adiponectin is a novel humoral vasodilator
Charité University Medicine Berlin, Germany
Medical Clinic for Nephrology and Internal Intensive Care, Campus Virchow Klinikum, 13353 Berlin, Germany
Franz Volhard Clinic at the Max Delbrück Center for Molecular Medicine, HELIOS Klinikum Berlin, 13125 Berlin, Germany
German Institute of Human Nutrition (DIFE) Potsdam-Rehbrücke, Max Rubner Laboratory, 14558 Nuthetal, Germany
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China
* Corresponding author. Medical Clinic for Nephrology and Internal Intensive Care, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. Tel.: +49 30 450 653 263; fax: +49 30 450 553 909. maik.gollasch{at}charite.de
Objectives Perivascular adipose tissue secretes an adipocyte-derived relaxing factor(s) (ADRF) that opens Kv channels in rat arteries. Visceral fat accumulation causes adipocyte dysfunction, including hyposecretion of adiponectin. We tested the hypothesis that ADRF might be adiponectin and that adiponectin plays a role in the paracrine control of vascular tone by perivascular adipose tissue.
Methods and results We studied Sprague–Dawley rats, wild-type and adiponectin gene-deficient (Apn 1–/–) mice, and New Zealand obese (NZO) mice. In rat aortas, recombinant adiponectin at serum levels (2–5 µg/ml) inhibited serotonin-induced contractions. The effects were abolished by Kv channel inhibition with 4-aminopyridine (4-AP, 2 mM). Similar effects were observed in NZO mouse mesenteric arteries. To study vascular function in Apn 1–/– mice, the mesenteric vascular bed was isolated, cannulated, and perfused at a constant 4–5-ml/min flow in the absence and presence of serotonin. 4-AP (2 mM) induced a similar increase in perfusion pressure in the Apn 1–/– perfused isolated mesenteric vascular bed, compared to wild-type mice. Removal of perivascular fat increased the vasoconstrictor responses, but abolished the 4-AP effects. The anti-contractile effects of perivascular fat were similar in mesenteric artery and aortic rings from Apn 1–/– and wild-type mice. Despite high adiponectin levels, the anti-contractile effects of perivascular fat were diminished in mesenteric arteries of NZO mice with age.
Conclusion Adiponectin is a novel humoral vasodilator that relaxes aortic and mesenteric rings by opening Kv channels. Similar to the rat, perivascular adipose tissue of the mouse harbors an ADRF, which is malfunctional in NZO mice and is not adiponectin.
KEYWORDS Adipocyte-derived relaxing factor; Adiponectin; Obesity; Vascular dysfunction; Hypertension; Kv channels