大鼠心脏慢性β-肾上腺素能受体刺激后α-肾上腺素能受体介导反应的增强
Potentiation of alpha-adrenoceptor-mediated responses following chronic beta-adrenoceptor stimulation in the rat heart.
作者信息
Butterfield M C, Chess-Williams R
机构信息
Department of Biomedical Science, University of Sheffield, Western Bank.
出版信息
Br J Pharmacol. 1993 Mar;108(3):658-62. doi: 10.1111/j.1476-5381.1993.tb12857.x.
Abstract
- Noradrenaline and isoprenaline were infused subcutaneously in rats by use of Alzet osmotic minipumps. The effects of catecholamine infusion on ventricular alpha- and beta-adrenoceptor density and also the responses of isolated cardiac tissues were compared with saline infusion. 2. Noradrenaline (1 mg kg-1) or isoprenaline (40 micrograms kg-1) infused for 3 days resulted in a desensitization of beta-adrenoceptor-mediated responses of isolated left atria and papillary muscles. Concentration-response curves to isoprenaline were shifted to the right in left atria whilst maximum responses were reduced in papillary muscles. Right atrial rate responses were not affected by infusions of catecholamines. 3. Infusions of either noradrenaline or isoprenaline resulted in a supersensitivity of alpha-adrenoceptor-mediated responses in isolated papillary muscles with leftward displacements of concentration-response curves to phenylephrine. 4. The density of both ventricular [3H]-dihydroalprenolol and [3H]-prazosin binding sites was reduced following noradrenaline infusion. Isoprenaline infusion reduced only the density of [3H]-dihydroalprenolol binding sites. 5. Noradrenaline infusion therefore 'down-regulates' both alpha- and beta-adrenoceptors in the rat heart but at the same time ventricular alpha-adrenoceptor-mediated responses are enhanced. Isoprenaline similarly enhances responses to phenylephrine and possible mechanisms for this phenomenon are discussed.
摘要
- 使用Alzet渗透微型泵将去甲肾上腺素和异丙肾上腺素皮下注射到大鼠体内。将儿茶酚胺注射对心室α和β肾上腺素能受体密度的影响以及分离的心脏组织的反应与生理盐水注射进行比较。2. 注射去甲肾上腺素（1 mg kg-1）或异丙肾上腺素（40 μg kg-1）3天导致分离的左心房和乳头肌中β肾上腺素能受体介导的反应脱敏。左心房中对异丙肾上腺素的浓度-反应曲线向右移动，而乳头肌中的最大反应降低。右心房率反应不受儿茶酚胺注射的影响。3. 去甲肾上腺素或异丙肾上腺素的注射导致分离的乳头肌中α肾上腺素能受体介导的反应超敏，对去氧肾上腺素的浓度-反应曲线向左移位。4. 注射去甲肾上腺素后，心室[3H]-二氢阿普洛尔和[3H]-哌唑嗪结合位点的密度均降低。注射异丙肾上腺素仅降低[3H]-二氢阿普洛尔结合位点的密度。5. 因此，注射去甲肾上腺素会使大鼠心脏中的α和β肾上腺素能受体“下调”，但同时心室α肾上腺素能受体介导的反应会增强。异丙肾上腺素同样增强了对去氧肾上腺素的反应，并讨论了这种现象的可能机制。
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