Hicks P E, Tierney C, Langer S Z
Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):388-95. doi: 10.1007/BF00692906.
Vasoconstrictor responses mediated by the alpha 2-adrenoceptor agonist TL99, were particularly sensitive to blockade by the calcium antagonist drug diltiazem in isolated perfused tail arteries of spontaneously hypertensive rats (SHR). In contrast, the vasoconstrictor responses induced by the alpha 1-adrenoceptor agonist methoxamine were significantly more resistant to antagonism by diltiazem. At higher concentrations (greater than 300 nmol/l) diltiazem became an effective antagonist of all alpha-adrenoceptor mediated responses. In normotensive Wistar Kyoto (WKY) or Sprague-Dawley (SD) rats diltiazem was significantly less potent against vasoconstrictor responses to TL99 than in SHR. The blockade of alpha 1-adrenoceptor mediated vasoconstriction by diltiazem was not significantly different when normotensive rats and SHR were compared. The vasoconstrictor responses evoked by 5HT in the perfused tail arteries were particularly resistant to blockade by diltiazem in SHR arteries. The responses to endogenously released noradrenaline, evoked by electrical field stimulation, were significantly antagonised by diltiazem (30 nmol/1-3 mumol/l) in SHR-tail arteries, while they were not modified in WKY-tail arteries. At the concentrations of diltiazem which blocked end organ responses to field stimulation, there was no modification of total tritium overflow from SHR-tail arteries after labelling the tissue with 3H-noradrenaline, indicating that diltiazem does not inhibit transmitter release at these concentrations. The tail artery preparation of SHR contains a population of postsynaptic alpha 2-adrenoceptors which mediate contraction in this blood vessel and the calcium entry blocker diltiazem is a potent antagonist of vasoconstrictor responses mediated by vascular alpha 2-adrenoceptors in hypertensive rats. These findings may be relevant to the antihypertensive action of diltiazem.
在自发性高血压大鼠（SHR）的离体灌注尾动脉中，由α2 -肾上腺素能受体激动剂TL99介导的血管收缩反应对钙拮抗剂地尔硫䓬的阻断作用尤为敏感。相比之下，α1 -肾上腺素能受体激动剂甲氧明诱导的血管收缩反应对地尔硫䓬的拮抗作用则明显更具抗性。在较高浓度（大于300 nmol/l）时，地尔硫䓬成为所有α -肾上腺素能受体介导反应的有效拮抗剂。在正常血压的Wistar Kyoto（WKY）或Sprague - Dawley（SD）大鼠中，地尔硫䓬对TL99引起的血管收缩反应的效力明显低于SHR。当比较正常血压大鼠和SHR时，地尔硫䓬对α1 -肾上腺素能受体介导的血管收缩的阻断作用没有显著差异。在SHR动脉中，5 -羟色胺（5HT）在灌注尾动脉中引起的血管收缩反应对地尔硫䓬的阻断作用特别具有抗性。电场刺激诱发的内源性去甲肾上腺素引起的反应在SHR尾动脉中被地尔硫䓬（30 nmol/l - 3 μmol/l）显著拮抗，而在WKY尾动脉中则未改变。在地尔硫䓬阻断终末器官对电场刺激反应的浓度下，用3H -去甲肾上腺素标记组织后，SHR尾动脉的总氚溢出量没有改变，这表明地尔硫䓬在这些浓度下不抑制递质释放。SHR的尾动脉制剂含有一群突触后α2 -肾上腺素能受体，它们介导该血管的收缩，钙通道阻滞剂地尔硫䓬是高血压大鼠血管α2 -肾上腺素能受体介导的血管收缩反应的有效拮抗剂。这些发现可能与地尔硫䓬的降压作用有关。
