Abstract

Increased sympathetic nervous system activity contributes to deoxycorticosterone acetate (DOCA)-salt hypertension in rats. ATP and norepinephrine (NE) are coreleased from perivascular sympathetic nerves. NE acts at prejunctional α₂-adrenergic receptors (α₂ARs) to inhibit NE release, and α₂AR function is impaired in DOCA-salt rats. Adenosine, an enzymatic ATP degradation product, acts at prejunctional A₁ adenosine receptors (A₁Rs) to inhibit NE release. We tested the hypothesis that prejunctional A₁R function is impaired in sympathetic nerves supplying mesenteric arteries (MAs) and veins (MVs) of DOCA-salt rats. Electrically evoked NE release and constrictions of blood vessels were studied in vitro with use of amperometry to measure NE oxidation currents and video microscopy, respectively. Immunohistochemical methods were used to localize tyrosine hydroxylase (TH) and A₁Rs in perivascular sympathetic nerves. TH and A₁Rs colocalized to perivascular sympathetic nerves. Adenosine and N⁶-cyclopentyl-adenosine (CPA, A₁R agonist) constricted MVs but not MAs. Adenosine and CPA (0.001–10 µM) inhibited neurogenic constrictions and NE release in MAs and MVs. DOCA-salt arteries were resistant to adenosine and CPA-mediated inhibition of NE release and constriction. The A_2A adenosine receptor agonist CGS21680 (C₂₃H₂₉N₇O₆.HCl.xH₂O) (0.001–0.1 μM) did not alter NE oxidation currents. We conclude that there are prejunctional A₁Rs in arteries and both pre- and postjunctional A₁Rs in veins; thus, adenosine selectively constricts the veins. Prejunctional A₁R function is impaired in arteries, but not veins, from DOCA-salt rats. Sympathetic autoreceptor dysfunction is not specific to α₂ARs, but there is a more general disruption of prejunctional mechanisms controlling sympathetic neurotransmitter release in DOCA-salt hypertension.