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Impaired alpha‐adrenergic autoreceptor modulation of purinergic transmission in mesenteric arteries of DOCA‐salt rats
Author(s) -
Demel Stacie Leigh,
Galligan James J
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a242-c
Subject(s) - mesenteric arteries , medicine , endocrinology , clonidine , purinergic receptor , excitatory postsynaptic potential , chemistry , receptor , artery
Hypertension is associated with an increase in NE and ATP release from sympathetic nerves associated with mesenteric arteries where ATP is the principal constrictor transmitter. Prejunctional α 2‐adrenoreceptors (ARs), regulate ATP and NE release. It is hypothesized that impairment of α 2 ‐AR function may cause increased ATP release contributing to arterial constriction and hypertension. Our goal was to determine whether impaired α 2 ‐AR function contributes to increased ATP release in mesenteric arteries of DOCA‐salt hypertensive rats. Mesenteric preparations were maintained in vitro and intracellular recordings of excitatory junction potentials (EJPs) from smooth muscle cells were recorded. EJPs, mediated by ATP acting at P2X1 receptors, were evoked using single electrical stimuli (10–100V). There were no differences in peak EJP amplitude recorded at any voltage from sham or DOCA‐salt arteries, nor were there differences in resting membrane potential or EJP rise/decay time. Clonidine (α 2 ‐AR agonist) caused a concentration dependent inhibition of EJPs in sham and DOCA‐salt arteries but EJPs in DOCA‐salt arteries was less sensitive to inhibition by clonidine (P < 0.05). Clonidine did not change ATP‐induced constrictions of sham arteries. However, clonidine caused direct constrictions of DOCA‐salt arteries. We conclude that DOCA‐salt hypertension does not modify the properties of arterial P2X 1 receptors. In addition, α 2 ‐ARs modulate ATP release and their function is impaired in DOCA‐salt hypertension. DOCA‐salt arteries are sensitized to the contractile effects of clonidine through an unidentified mechanism.