Short-term aortic barodenervation diminishes alpha(1)-adrenoceptor reactivity in rat aortic smooth muscle
Short-term aortic barodenervation diminishes alpha(1)-adrenoceptor reactivity in rat aortic smooth muscle
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DOI：
10.1016/s0014-2999(97)00010-1
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发表时间：
1997-03-19
影响因子：
5
通讯作者：
Daabees, TT
中科院分区：
文献类型：
--
作者：
ElMas, MM;AbdelGalil, AGA;Daabees, TT
我们以前的研究表明，主动脉压力感受器去神经引起血压急性升高，交感神经活性和外周血管阻力显著升高。本研究探讨了短期（3和48小时）的影响，主动脉压力神经和相关的交感神经亢进的功能活动的α（1）-肾上腺素受体在大鼠主动脉平滑肌。与假手术组相比，去主动脉压力神经组大鼠血压和心率明显升高，压力反射敏感性降低。血压和心率仍然升高时，在清醒的主动脉压力失神经大鼠手术后3小时测量，但在48小时消退到假手术的水平，压力反射敏感性，但是，仍然衰减。六甲铵（0.5-4 mg/kg，i. v.）在清醒的主动脉去压力神经大鼠中，在3和48 h均引起显著（P < 0.05）的降压反应，提示去神经大鼠的交感神经活性更高。将主动脉去压力神经和假手术大鼠的主动脉环暴露于苯肾上腺素（α（1）-肾上腺素能受体激动剂，3 × 10（-8）-1 × 10（-4）M）的累积添加物中，导致两组大鼠在3 h时相似的浓度相关收缩反应，而在48 h时去神经大鼠的主动脉环收缩明显较小（P < 0.05）。与假手术大鼠相比，48 h时出现的最大收缩（E（max））显示去压力神经支配的主动脉环减少约50%（239 +/- 16 vs. 558 +/- 15 mg张力/mg组织）。哌唑嗪（α 1-肾上腺素能受体拮抗剂）的pA 2值在3 h时不受主动脉去压力神经支配的影响，但在48 h时与假手术值相比显著增加（P < 0.05）。结论：短期主动脉去压力神经支配导致交感神经活性升高，这与主动脉平滑肌对α（1）-肾上腺素能受体激活的反应性降低一致。主动脉去压力神经诱导的α（1）-肾上腺素受体脱敏不是受体亲和力降低的结果，但可能涉及受体密度的改变或受体后激活事件。(C)1997年Elsevier Science B.V.
Our previous studies have shown that aortic baroreceptor denervation elicits acute increases in blood pressure and significant elevations of sympathetic activity and peripheral vascular resistance. This study investigated the short-term (3 and 48 h) effect of aortic barodenervation and associated sympathetic hyperactivity on the functional activity of alpha(1)-adrenoceptors in rat aortic smooth muscle. Compared with sham operation, aortic barodenervation caused acute rises in blood pressure and heart rate and reductions in baroreflex sensitivity. Blood pressure and heart rate remained elevated when measured in conscious aortic barodenervated rats 3 h after surgery but subsided to sham-operated levels at 48 h; the baroreflex sensitivity, however, remained attenuated. Hexamethonium (0.5-4 mg/kg, i.v.) elicited significantly (P < 0.05) greater depressor responses in conscious aortic barodenervated rats than in sham-operated rats at both 3 and 48 h, suggesting a higher sympathetic activity in denervated rats. Exposure of aortic rings from aortic barodenervated and sham-operated rats to cumulative addition of phenylephrine (alpha(1)-adrenoceptor agonist, 3 X 10(-8)-1 x 10(-4) M) resulted in concentration-related contractile responses that were similar in the two groups of rats at 3 h in contrast to significantly (P < 0.05) smaller contractions in rings from denervated rats at 48 h. The maximum contraction developed( E(max)) at 48 h showed approximately 50% reduction in rings from aortic barodenervated compared with sham-operated rats (239 +/- 16 vs. 558 +/- 15 mg tension/mg tissue). The pA(2) value for prazosin (alpha(1)-adrenoceptor antagonist) was not altered by aortic barodenervation at 3 h but showed significant (P < 0.05) increases, compared with sham-operated values, at 48 h. It is concluded that short-term aortic barodenervation results in an elevation of sympathetic activity that coincides with reduced responsiveness of aortic smooth muscle to alpha(1)-adrenoceptor activation. The aortic barodenervation-induced alpha(1)-adrenoceptor desensitization is not a result of decreased receptor affinity but may involve an alteration of receptor density or in the post-receptor activation events. (C) 1997 Elsevier Science B.V.