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Am J Physiol Heart Circ Physiol 286: H1558-H1564, 2004. First published December 11, 2003; doi:10.1152/ajpheart.00592.2003
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Impaired function of {alpha}2-adrenergic autoreceptors on sympathetic nerves associated with mesenteric arteries and veins in DOCA-salt hypertension

Min Luo, Gregory D. Fink, Keith J. Lookingland, John A. Morris, and James J. Galligan

Department of Pharmacology and Toxicology and the Neuroscience Program, Michigan State University, East Lansing, Michigan 48824

Submitted 23 June 2003 ; accepted in final form 4 December 2003

The present study tested the hypothesis that there is impaired function of {alpha}2-adrenergic autoreceptors and increased transmitter release from sympathetic nerves associated with mesenteric arteries and veins from DOCA-salt rats. High-performance liquid chromatography was used to measure the overflow of ATP and norepinephrine (NE) from electrically stimulated mesenteric artery and vein preparations in vitro. In sham arteries, nerve stimulation evoked a 1.5-fold increase in NE release, whereas in DOCA-salt arteries there was a 3.9-fold increase in NE release over basal levels (P < 0.05). In contrast, stimulated ATP release was not different in DOCA-salt arteries compared with sham arteries. In sham veins, nerve stimulation evoked a 2.9-fold increase in NE release, whereas in DOCA-salt veins there was a 8.4-fold increase in NE release over basal levels (P < 0.05). In sham rats NE release, normalized to basal levels, was greater in veins than in arteries (P < 0.05). The {alpha}2-adrenergic receptor antagonist yohimbine (1 µM) increased ATP and NE release in sham but not DOCA-salt arteries. The {alpha}2-adrenergic receptor agonist UK-14,304 (10 µM) decreased ATP release in sham but not DOCA-salt arteries. In sham veins, UK-14,304 decreased, but yohimbine increased, NE release; effects that were not observed in DOCA-salt veins. These data show that nerve stimulation causes a greater increase in NE release from nerves associated with veins compared with arteries. In addition, impairment of {alpha}2-adrenergic autoreceptor function in sympathetic nerves associated with arteries and veins from DOCA-salt rats results in increased NE release.

norepinephrine; ATP; vasoconstriction; splanchnic circulation



Address for reprint requests and other correspondence: J. J. Galligan, Dept. of Pharmacology and Toxicology and the Neuroscience Program, Life Science B400, Michigan State Univ., East Lansing, MI 48824 (E-mail: galliga1{at}msu.edu).




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