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Mechanisms of ADRF release from rat aortic adventitial adipose tissue

Item Type:Article
Title:Mechanisms of ADRF release from rat aortic adventitial adipose tissue
Creators Name:Dubrovska, G. and Verlohren, S. and Luft, F.C. and Gollasch, M.
Abstract:Blood vessels are surrounded by variable amounts of adipose tissue. We showed earlier that adventitial adipose tissue inhibits rat aortic contraction by release of a transferable factor, adventitium-derived relaxing factor (ADRF), which activates smooth muscle K(+) channels. However, little is known about the mechanisms of ADRF release. Using isolated rat aortic rings and isometric contraction measurements, we show that ADRF release depends on extracellular [Ca(2+)] (EC(50) ∼ 4.7 mM). ADRF effects do not involve neuronal presynaptic N-type Ca(2+) and Na(+) channels or vanilloid, cannabinoid, and CGRP receptors. ADRF release is strongly inhibited by the protein tyrosine kinase inhibitors genistein and tyrphostin A25. In contrast, daidzein, an inactive genistein analog, and the protein tyrosine kinase inhibitor ST638 had no effect. Protein kinase A inhibition by H89 also inhibited ADRF release, whereas the protein kinase G inhibitor KT-5823 had no effect. We propose that ADRF release is Ca(2+) dependent and is regulated by intracellular signaling pathways involving tyrosine kinase and protein kinase A. Furthermore, ADRF release does not depend on perivascular nerve endings.
Keywords:Adipose Tissue, Aorta, Blood Pressure, Calcitonin Gene-Related Peptide Receptors, Calcium, Calcium Channels, Cannabinoid Receptors, Cyclic AMP-Dependent Protein Kinases, Drug Receptors, Endothelium-Dependent Relaxing Factors, Intracellular Signaling Peptides and Proteins, Muscle Contraction, Protein-Serine-Threonine Kinases, rho-Associated Kinases, Sprague-Dawley Rats, Signal Transduction, Sodium Channels, Animals, Rats
Source:American Journal of Physiology Heart and Circulatory Physiology
ISSN:0363-6135
Publisher:American Physiological Society (U.S.A.)
Volume:286
Number:3
Page Range:H1107-H1113
Date:1 January 2004
Official Publication:https://doi.org/10.1152/ajpheart.00656.2003
PubMed:View item in PubMed

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