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(Hypertension. 2008;52:322.)
© 2008 American Heart Association, Inc.

Original Articles

Impaired Purinergic Neurotransmission to Mesenteric Arteries in Deoxycorticosterone Acetate-Salt Hypertensive Rats

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

Correspondence to Stacie L. Demel, Neuroscience Program, B328 Life Science Building, Michigan State University, East Lansing, MI 48824. E-mail demelsta{at}msu.edu

Sympathetic nerves release norepinephrine and ATP onto mesenteric arteries. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats, there is increased arterial sympathetic neurotransmission attributable, in part, to impaired prejunctional regulation of norepinephrine release. Prejunctional regulation purinergic transmission in hypertension is less well understood. We hypothesized that ₂-adrenergic receptor dysfunction alters purinergic neurotransmission to arteries in DOCA-salt hypertensive rats. Mesenteric artery preparations were maintained in vitro, and intracellular electrophysiological methods were used to record excitatory junction potentials (EJPs) from smooth muscle cells. EJP amplitude was reduced in smooth muscle cells from DOCA-salt (4±1 mV) compared with control arteries (9±1 mV; P<0.05). When using short trains of stimulation (0.5 Hz; 5 pulses), the ₂adrenergic receptor antagonist yohimbine (1 µmol/L) potentiated EJPs in control more than in DOCA-salt arteries (180±35% versus 86±7%; P<0.05). Norepinephrine (0.1 to 3.0 µmol/L), the ₂adrenergic receptor agonist UK 14304 (0.001 to 0.100 µmol/L), the A₁ adenosine receptor agonist cyclopentyladensosine (0.3 to 100.0 µmol/L), and the N-type calcium channel blocker -conotoxin GVIA (0.0003 to 0.1000 µmol/L) decreased EJP amplitude equally well in control and DOCA-salt arteries. Trains of stimuli (10 Hz) depleted ATP stores more completely, and the latency to EJP recovery was longer in DOCA-salt compared with control arteries. These data indicate that there is reduced purinergic input to mesenteric arteries of DOCA-salt rats because of decreased ATP bioavailability in sympathetic nerves. These data highlight the potential importance of impaired purinergic regulation of arterial tone as a target for drug treatment of hypertension.

Key Words: sympathetic nervous system • excitatory junction potential • vascular neuroeffector junction • ATP • P2X receptors