Periadventitial fat releases a vascular relaxing factor.
Virtually all blood vessels are surrounded by adventitial fat. Adipocytes produce a host of vasoactive substances that may influence vascular contraction. We tested whether or not perivascular adipose tissue modulates contraction of aortic ring preparations. We studied aortic rings surrounded by periadventitial adipose tissue from adult Sprague-Dawley rats. At a maximum concentration of 300 nM angiotensin II, 6.5 microM serotonin, and 5 microM phenylephrine, the contractile response of intact rings was 95%, 80%, and 30% lower than that of vessels without periadventitial fat. The anticontractile effect of periadventitial fat was reduced by inhibition of ATP-dependent K+ channels with glibenclamide (3 microM) and by the tyrosine kinase inhibitor genistein (10 microM). Blocking NOS, cyclo-oxygenase, cytochrome P450, or adenosine receptors did not restore the vascular response in intact vessels. The anticontractile effect of perivascular fat was present in Zucker fa/fa rats, suggesting that leptin receptors were not responsible. Transferring the bath solution from intact vessels, isolated periadventitial tissue, and cultured rat adipocytes to precontracted vessels lacking periadventitial fat resulted in a rapid relaxation. We suggest that perivascular adventitial adipose tissue releases a transferable adventitium-derived relaxing factor that acts by tyrosine kinase-dependent activation of K+ channels in vascular smooth muscle cells.
Löhn
Matthias
M
HELIOS Klinikum Berlin, Franz Volhard Clinic and Max Delbrück Center for Molecular Medicine, Medical Faculty of the Charité, Humboldt University of Berlin, Germany.
Dubrovska
Galyna
G
Lauterbach
Birgit
B
Luft
Friedrich C
FC
Gollasch
Maik
M
Sharma
Arya M
AM
D017667:Adipocytes / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000502:physiology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001681:Biological Assay; D002460:Cell Line; D002478:Cells, Cultured; D018920:Coculture Techniques; D046508:Culture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D005905:Glyburide / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D005905:Glyburide