Impaired function of alpha2-adrenergic autoreceptors on sympathetic nerves associated with mesenteric arteries and veins in DOCA-salt hypertension.
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 microM) increased ATP and NE release in sham but not DOCA-salt arteries. The alpha(2)-adrenergic receptor agonist UK-14304 (10 microM) decreased ATP release in sham but not DOCA-salt arteries. In sham veins, UK-14304 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.
Luo
Min
M
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Fink
Gregory D
GD
Lookingland
Keith J
KJ
Morris
John A
JA
Galligan
James J
JJ
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D017660:Autoreceptors / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003900:Desoxycorticosterone; D004558:Electric Stimulation; D004563:Electrochemistry; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008638:Mesenteric Arteries / Q000294:innervation* / Q000503:physiopathology*; D008642:Mesenteric Veins / Q000294:innervation* / Q000503:physiopathology*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D012965:Sodium Chloride; D013050:Spectrometry, Fluorescence; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D000227:Adenine Nucleotides; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D017660:Autoreceptors; D018341:Receptors, Adrenergic, alpha-2; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D000255:Adenosine Triphosphate; D000241:Adenosine; D009638:Norepinephrine