Periadventitial fat releases a vascular relaxing factor

• Published in: The FASEB journal 2002-07, Vol.16 (9), p.1057-1063
• Main Authors: LÖHN, MATTHIAS, DUBROVSKA, GALYNA, LAUTERBACH, BIRGIT, LUFT, FRIEDRICH C., GOLLASCH, MAIK, SHARMA, ARYA M.
• Format: Article
• Language: English
• Subjects: Adipocytes - metabolism; Adipose Tissue - metabolism; Adipose Tissue - physiology; adventitium; Animals; Aorta - drug effects; Aorta - physiology; Biological Assay; Cell Line; Cells, Cultured; Coculture Techniques; Culture Techniques; Enzyme Inhibitors - pharmacology; fat; Genistein - pharmacology; Glyburide - pharmacology; ion channels; Kinetics; Male; Mice; Potassium Channel Blockers - pharmacology; Protein-Tyrosine Kinases - antagonists & inhibitors; Rats; Rats, Sprague-Dawley; tyrosine phosphorylation; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology; Vasodilator Agents - metabolism; Vasodilator Agents - pharmacology
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.02-0024com

ABSTRACT 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 μM serotonin, and 5 μM phenyleph‐rine, the contractile response of intact rings was 95%, 80%, and 30% lower than that of vessels without periadventitial fat. The anticontractile effect of periad‐ventitial fat was reduced by inhibition of ATP‐dependent K+ channels with glibenclamide (3 μM) and by the tyrosine kinase inhibitor genistein (10 μM). 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, M., Dubrovska, G., Lauterbach, B., Luft, F. C., Gollasch, M., Sharma, A. M. Periadventitial fat releases a vascular relaxing factor. FASEB J. 16, 1057–1063 (2002)