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Am J Physiol Heart Circ Physiol 283: H1523-H1530, 2002. First published June 20, 2002; doi:10.1152/ajpheart.00177.2001
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Vol. 283, Issue 4, H1523-H1530, October 2002

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

Dan Hoang, Heather Macarthur, Alice Gardner, and Thomas C. Westfall

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 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.

sympathetic neurotransmission


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