Adiponectin is a novel humoral vasodilator.
OBJECTIVE
Perivascular adipose tissue secretes an adipocyte-derived relaxing factor(s) (ADRF) that opens K(v) 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.


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 microg/ml) inhibited serotonin-induced contractions. The effects were abolished by K(v) 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.


CONCLUSIONS
Adiponectin is a novel humoral vasodilator that relaxes aortic and mesenteric rings by opening K(v) channels. Similar to the rat, perivascular adipose tissue of the mouse harbors an ADRF, which is malfunctional in NZO mice and is not adiponectin.
Fésüs
Gábor
G
Charité University Medicine Berlin, Germany.
Dubrovska
Galyna
G
Gorzelniak
Kerstin
K
Kluge
Reinhart
R
Huang
Yu
Y
Luft
Friedrich C
FC
Gollasch
Maik
M
D015761:4-Aminopyridine / Q000494:pharmacology; D052242:Adiponectin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000375:Aging / Q000378:metabolism; D000818:Animals; D001011:Aorta; D015870:Gene Expression; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009765:Obesity / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D052242:Adiponectin; D026902:Potassium Channel Blockers; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011994:Recombinant Proteins; D014665:Vasodilator Agents; C475419:adiponectin receptor 1, mouse; D012701:Serotonin; D015761:4-Aminopyridine