Endothelin-induced modulation of neuropeptide Y and norepinephrine release from the rat mesenteric bed

• Published in: American journal of physiology. Heart and circulatory physiology 2002-10, Vol.283 (4), p.H1523-H1530
• Main Authors: Hoang, Dan, Macarthur, Heather, Gardner, Alice, Westfall, Thomas C
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive Agents - pharmacology; Electric Stimulation; Endothelin Receptor Antagonists; Endothelin-1 - pharmacology; Endothelin-3 - pharmacology; Male; Mesenteric Arteries - innervation; Mesenteric Arteries - metabolism; Neuropeptide Y - metabolism; Norepinephrine - metabolism; Oligopeptides - pharmacology; Peptides, Cyclic - pharmacology; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System - drug effects; Sympathetic Nervous System - metabolism; Vasoconstrictor Agents - pharmacology; Viper Venoms - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00177.2001

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104 The effect of three endothelin (ET) agonists [ET-1, ET-3, and sarafotoxin (STX6C)] on the nerve stimulation-induced release of norepinephrine (NE) and neuropeptide Y-immunoreactive compounds (NPY-ir) from the perfused mesenteric arterial bed of the rat as well as the effect on perfusion pressure were examined. ET-1, ET-3, and STX6C all produced a significant, concentration-dependent decrease in the evoked release of NPY-ir but had no effect on the release of NE. In contrast, all three ETs potentiated the nerve stimulation-induced increase in perfusion pressure. The inhibition of nerve stimulation-induced NPY-ir release by ET-1 was significantly blocked by the ET A /ET B antagonist PD-142893 and the ET B antagonist RES-701-1 but not by the ET A antagonist BQ-123. The potentiation of the nerve stimulation-induced increase in perfusion pressure by ET-1 was significantly blocked by PD-142893 and BQ-123 and attenuated by RES-701-1. Prior exposure of the preparation to indomethacin or meclofenamate failed to alter the attenuation of the evoked release of NPY-ir or the potentiation of the increase in perfusion pressure produced by ET-1 or ET-3. These results are consistent with the idea that sympathetic cotransmitters can be preferentially modulated by paracrine mediators at the vascular neuroeffector junction. sympathetic neurotransmission