Demel Stacie L, Galligan James J
Neuroscience Program, B328 Life Science Building, Michigan State University, East Lansing, MI 48824, USA.
Hypertension. 2008 Aug;52(2):322-9. doi: 10.1161/HYPERTENSIONAHA.108.110353. Epub 2008 Jul 7.
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 alpha(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 alpha(2)adrenergic receptor antagonist yohimbine (1 micromol/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 micromol/L), the alpha(2)adrenergic receptor agonist UK 14304 (0.001 to 0.100 micromol/L), the A(1) adenosine receptor agonist cyclopentyladensosine (0.3 to 100.0 micromol/L), and the N-type calcium channel blocker omega-conotoxin GVIA (0.0003 to 0.1000 micromol/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.
交感神经将去甲肾上腺素和三磷酸腺苷释放到肠系膜动脉上。在醋酸脱氧皮质酮（DOCA）-盐性高血压大鼠中，动脉交感神经传递增加，部分原因是去甲肾上腺素释放的节前调节受损。高血压中嘌呤能传递的节前调节了解较少。我们假设α₂-肾上腺素能受体功能障碍会改变DOCA-盐性高血压大鼠动脉的嘌呤能神经传递。将肠系膜动脉标本维持在体外，采用细胞内电生理方法记录平滑肌细胞的兴奋性接头电位（EJP）。与对照动脉（9±1 mV）相比，DOCA-盐组平滑肌细胞的EJP幅度降低（4±1 mV；P<0.05）。当使用短串刺激（0.5 Hz；5个脉冲）时，α₂-肾上腺素能受体拮抗剂育亨宾（1 μmol/L）增强对照动脉EJP的作用比DOCA-盐动脉更明显（180±35%对86±7%；P<0.05）。去甲肾上腺素（0.1至3.0 μmol/L）、α₂-肾上腺素能受体激动剂UK 14304（0.001至0.100 μmol/L）、A₁腺苷受体激动剂环戊基腺苷（0.3至100.0 μmol/L）和N型钙通道阻滞剂ω-芋螺毒素GVIA（0.0003至0.1000 μmol/L）在对照动脉和DOCA-盐动脉中同等程度地降低EJP幅度。串刺激（10 Hz）更完全地耗尽了三磷酸腺苷储备，与对照动脉相比，DOCA-盐动脉中EJP恢复的潜伏期更长。这些数据表明，由于交感神经中三磷酸腺苷生物利用度降低，DOCA-盐大鼠肠系膜动脉的嘌呤能输入减少。这些数据突出了嘌呤能对动脉张力调节受损作为高血压药物治疗靶点的潜在重要性。
