Kahan T, Hjemdahl P
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
J Cardiovasc Pharmacol. 1987 Oct;10(4):433-8. doi: 10.1097/00005344-198710000-00008.
Prejunctional beta-adrenoceptor-mediated modulation of sympathetic neurotransmission was studied in desipramine-pretreated canine blood-perfused gracilis muscle. Overflow of endogenous noradrenaline (NA) to venous plasma and vasoconstriction reflect pre- and postjunctional events in this in vivo model. The nonselective beta-adrenoceptor agonist isoprenaline (15 nM in arterial plasma) and the beta 2-selective agonist rimiterol (50 nM) caused similar vasodilatation (35-40% increase in vascular conductance, p less than 0.01), enhancement of nerve stimulation-evoked vasoconstriction (+20-25%, p less than 0.01), and NA overflow (+13%, p less than 0.05). Isoprenaline, 3 nM, evoked vasodilatation but did not alter NA overflow. Blockade of beta 2-adrenoceptors by ICI 118,551 increased basal vascular tone (+9%, p less than 0.01) and reduced nerve stimulation-evoked vasoconstriction (-7%, p less than 0.05), but failed to alter NA overflow significantly (-12%, p = 0.12). ICI 118,551 blocked all responses to the beta-adrenoceptor agonists. Thus, prejunctional beta 2-adrenoceptor-mediated facilitation of sympathetic neurotransmission could be demonstrated in vivo, but the effects were modest. Previous experiments, however, have demonstrated a considerably larger influence of alpha-adrenoceptor-mediated prejunctional modulation in this model. Hence, prejunctional modulation via beta-adrenoceptors appears to be of subordinate importance when compared with the alpha-adrenoceptor-mediated inhibitory mechanism under these physiological conditions.
在经地昔帕明预处理的犬血液灌注股薄肌中，研究了接头前β-肾上腺素能受体介导的交感神经传递调节。内源性去甲肾上腺素（NA）向静脉血浆的溢出和血管收缩反映了该体内模型中的接头前和接头后事件。非选择性β-肾上腺素能受体激动剂异丙肾上腺素（动脉血浆中为15 nM）和β2选择性激动剂瑞米特罗（50 nM）引起相似的血管舒张（血管传导增加35 - 40%，p < 0.01）、增强神经刺激诱发的血管收缩（+20 - 25%，p < 0.01）以及NA溢出增加（+13%，p < 0.05）。3 nM的异丙肾上腺素引起血管舒张，但未改变NA溢出。ICI 118,551阻断β2-肾上腺素能受体增加了基础血管张力（+9%，p < 0.01）并减少了神经刺激诱发的血管收缩（-7%，p < 0.05），但未能显著改变NA溢出（-12%，p = 0.12）。ICI 118,551阻断了对β-肾上腺素能受体激动剂的所有反应。因此，接头前β2-肾上腺素能受体介导的交感神经传递促进作用在体内可以得到证实，但作用较小。然而，先前的实验表明在该模型中α-肾上腺素能受体介导的接头前调节影响要大得多。因此，在这些生理条件下，与α-肾上腺素能受体介导的抑制机制相比，通过β-肾上腺素能受体的接头前调节似乎次要。
