Arteriolar constriction to alpha(2)-adrenergic agonist dexmedetomidine in the rat
Arteriolar constriction to alpha(2)-adrenergic agonist dexmedetomidine in the rat
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DOI：
10.1152/ajpheart.1997.272.6.h2547
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发表时间：
1997-06-01
影响因子：
4.8
通讯作者：
McPherson, RW
中科院分区：
文献类型：
--
作者：
Asano, Y;Koehler, RC;McPherson, RW
右美托咪定（Dex）是一种α（2）-肾上腺素能激动剂，全身给药时可降低脑血流量（CBF）。目前还不清楚脑血管收缩是通过对脑血管的局部作用还是通过远程神经机制介导的。在本研究中，我们比较了软膜小动脉对局部和全身给药Dex的反应，局部应用和不应用特异性α（2）-肾上腺素能拮抗剂阿替美唑。用异氟烷麻醉6组雄性大鼠（每组n = 7），准备通过活体显微镜测量小（20-39 μ m）、中（40-59 μ m）和大（60-79 μ m）软脑膜小动脉直径，或通过放射性标记微球法测量局部CBF。局部应用Dex引起剂量依赖性收缩，对于小型和中型小动脉，在10（-8）M时开始显著收缩，对于大型小动脉，在10（-7）M时开始显著收缩。局部应用10（-4）M阿替美唑几乎完全阻断了小[21 +/- 2%（SE）]、中等（21 +/- 2%）和大（15 +/- 1%）小动脉中10（-5）M的收缩。静脉注射1 μ g/kg Dex可降低CBF，并引起轻度小动脉收缩，给药后8分钟开始消退。10 μ g/kg剂量使各种大小的小动脉收缩，约10分钟后收缩开始消退。局部应用阿替美唑（10（-4）M）可轻微减弱对1 μ g/kg静脉注射Dex的反应，但10 μ g/kg后基本上不限制收缩。这些数据表明软膜小动脉能够通过局部α（2）-肾上腺素能机制对Dex产生实质性收缩。然而，局部应用阿替美唑不能显著抑制全身给予Dex的血管收缩反应，表明Lex也可能通过在中枢神经系统其他部位的作用间接引起血管收缩。
Dexmedetomidine (Dex) is an alpha(2)-adrenergic agonist that decreases cerebral blood flow (CBF) when administered systemically. It is unclear whether cerebral vasoconstriction is mediated by a local effect on cerebral vessels or by a remote neural mechanism. In the present study, we compared the pial arteriole responses to locally and systemically administered Dex with and without local application of the specific alpha(2)-adrenergic antagonist atipamezole. Six groups of male rats (n = 7 each) were anesthetized with isoflurane and prepared for measurements of small (20-39 mu m), medium (40-59 Fern), and large (60-79 mu m) pial arteriole diameter by intravital microscopy or for regional CBF measurement by the radiolabeled-microsphere method. Local application of Dex caused dose-dependent constriction that was significant starting at 10(-8) M for small and medium-sized arterioles and at 10(-7) M for large arterioles. Constriction to 10(-5) M in small [21 +/- 2% (SE)], medium (21 +/- 2%), and large (15 +/- 1%) arterioles was almost completely blocked by local application of 10(-4) M atipamezole. Intravenous administration of Dex at 1 mu g/kg decreased CBF and caused modest arteriolar constriction that began to resolve 8 min after administration. A dose of 10 mu g/kg constricted arterioles of all sizes with constriction beginning to resolve after similar to 10 min. Local application of atipamezole (10(-4) M) slightly blunted the response to 1 mu g/kg of intravenous Dex but did not substantially limit constriction after 10 mu g/kg. These data demonstrate that pial arterioles are capable of substantial constriction to Dex by a local alpha(2)-adrenergic mechanism. However, the inability of locally applied atipamezole to substantially inhibit the vasoconstrictor response to systemically administered Dex suggests that Lex might also cause vasoconstriction indirectly through actions at other sites in the central nervous system.