Beta-adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field.
Beta-adrenoceptor antagonists suppress elevation in body temperature and increase in plasma IL-6 in rats exposed to open field.
复制标题
β-肾上腺素受体拮抗剂可抑制暴露于旷场的大鼠的体温升高和血浆 IL-6 的增加。
DOI：
10.1159/000127072
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发表时间：
1996
影响因子：
4.1
通讯作者：
Kluger,MJ
中科院分区：
文献类型：
--
作者：
Soszynski,D;Kozak,W;Conn,CA;Rudolph,K;Kluger,MJ
这些研究的目的是评估β肾上腺素受体在心理应激引起的体温升高(TB)和循环白介素6(IL-6)升高中的作用。我们选择了三种试图阻断体温和血浆IL-6升高的药物：L-心得安、D-心得安和纳多洛尔。普萘洛尔的两种立体异构体都具有局部麻醉的膜稳定活性，并能够渗透到大脑中。但D-心得安对β的阻断作用明显低于L心得安。纳多洛尔具有类似L-普萘洛尔的β阻断活性，但不具有稳定膜的活性。此外，纳多洛尔不能越过血脑屏障。所有β阻滞剂均经腹膜腔注射(Ip)。7.5 mg/kg)或第三脑室注射(i.c.v，5或50微克/只)，20分钟或就在大鼠暴露于开阔场地之前。大鼠暴露于野外后立即采血测定血浆IL-6活性(IL-6依赖的B9细胞生物测定法)。暴露在野外后，没有接受β阻滞剂治疗的大鼠的反应是通过生物遥测测量Tb迅速上升，以及血浆IL-6活性增加。腹腔注射L心得安可显著抑制旷场暴露大鼠血脑屏障的升高。(L心得安组ΔTmax=0.14±0.15°C，赋形剂组为0.78±0.15°C)。两个都不是IP。注射D-心得安或纳多洛尔对暴露于开阔场地所致的Tb升高无影响。两人都是I.C.V.剂量的L心得安和纳多洛尔显著减弱野外诱发的结核病上升。大的I.C.V。剂量D-心得安(50µg)可抑制Tbin暴露大鼠的血压升高，而小剂量(5µg)则不能抑制Tbin野外暴露大鼠的血压升高。暴露于野外的大鼠注射L心得安(均为I.P.或I.C.V.)血浆IL-6活性低于空场注射Vehicle组(P<0.05)。注射用L心得安为5.2±1.3U/ml，溶媒为17.4±3.8U/ml，静脉注射为17.4±3.8U/ml。注射用L心得安为3.5±2.3U/ml，溶媒为24.4±7.2U/ml)。纳多洛尔只有在静脉注射时才能阻断开放视野引起的血浆IL-6升高。但不是IP。两个都不是IP。也不是静脉注射。D-心得安对旷场暴露大鼠血浆IL-6活性有影响。这些数据表明，中枢神经系统中的β肾上腺素受体参与了心理应激引起的T波段升高以及暴露于开阔场地引起的血浆IL-6活性升高。
The purpose of these studies was to assess the involvement of β-adrenoceptors in the development of psychological stress-induced elevation in body temperature (Tb) and rise in circulating interleukin-6 (IL-6). We selected three drugs to attempt to block the rise in body temperature and plasma IL-6; L-propranolol, D-propranolol and nadolol. Both stereoisomers of propranolol have ‘local anesthetic’ membrane-stabilizing activity and are capable of penetrating into the brain. However, D-propranolol has significantly lower β-blocking activity than L-propranolol. Nadolol has β-blocking activity similar to L-propranolol without membrane-stabilizing activity. Furthermore, nadolol does not cross the blood-brain barrier. All β-blockers were injected intraperitoneally (i.p. 7.5 mg/kg) or into the third cerebral ventricle (i.c.v., 5 or 50 µg/animal), 20 min or just before exposure of rats to an open field, respectively. Blood samples for measurement of plasma IL-6 activity (IL-6-dependent B9 cell bioassay) were taken from rats immediately following exposure to the open field. After exposure to the open field, rats not treated with β-blockers responded with a rapid rise in Tbmeasured by biotelemetry as well as with an increase in plasma IL-6 activity. The increase in Tbof open field-exposed rats was significantly suppressed by L-propranolol injected i.p. (ΔTmax= 0.14 ± 0.15°C for L-propranolol vs. 0.78 ± 0.15°C for vehicle-treated rats). Neither i.p. injection of D-propranolol nor nadolol had any effect on the increase in Tbinduced by exposure to the open field. Both i.c.v. doses of L-propranolol and nadolol markedly attenuated the open field-induced rise in Tb. The large i.c.v. dose of D-propranolol (50 µg) did, whereas the lower dose (5 µg) did not suppress the elevation in Tbin open field exposed rats. The open field-exposed rats injected with L-propranolol (both i.p. or i.c.v.) had lower plasma IL-6 activity than that of open field-exposed rats injected with vehicle (for i.p. injection: 5.2 ± 1.3 U/ml for L-propranolol vs. 17.4 ± 3.8 U/ml for vehicle; for i.c.v. injection: 3.5 ± 2.3 U/ml for L-propranolol vs. 24.4 ± 7.2 U/ml for vehicle). Nadolol blocked the open field-induced rise in plasma IL-6 only when injected i.c.v. but not i.p. Neither i.p. nor i.c.v. D-propranolol injection had an effect on plasma IL-6 activity in open field-exposed rats. These data show that β-adrenoceptors in the central nervous system are involved in the psychological stress-induced elevation in Tband rise in plasma IL-6 activity caused by exposure to an open field.