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.52 (4), p.H1523-H1530
• Main Authors: HOANG, Dan, MACARTHUR, Heather, GARDNER, Alice, WESTFALL, Thomas C
• Format: Article
• Language: English
• Subjects: Anatomy & physiology; Biological and medical sciences; Blood vessels and receptors; Fundamental and applied biological sciences. Psychology; Neurotransmitters; Vertebrates: cardiovascular system
• ISSN: 0363-6135; 1522-1539

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 ETA/ETB antagonist PD-142893 and the ETB antagonist RES-701-1 but not by the ETA 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.