Mechanisms of ADRF release from rat aortic adventitial adipose tissue.
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) approximately 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.
Dubrovska
Galyna
G
Franz Volhard Clinic, Wiltbergstrasse 50, 13125 Berlin, Germany.
Verlohren
Stefan
S
Luft
Friedrich C
FC
Gollasch
Maik
M
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D045462:Endothelium-Dependent Relaxing Factors / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D043882:Receptors, Cannabinoid / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015222:Sodium Channels / Q000378:metabolism; D054460:rho-Associated Kinases
D015220:Calcium Channels; D045462:Endothelium-Dependent Relaxing Factors; D047908:Intracellular Signaling Peptides and Proteins; D018015:Receptors, Calcitonin Gene-Related Peptide; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D015222:Sodium Channels; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium