Vargas H M, Zhou L, Gorman A J
Hoechst-Roussel Pharmaceuticals, Inc., Neuroscience Business Unit, Somerville, New Jersey.
J Pharmacol Exp Ther. 1994 Nov;271(2):748-54.
Previous studies suggest that systemic arterial pressure is tonically regulated by the interaction of peripheral sympathetic nerves with vascular alpha-1A adrenoceptors in vivo. To explore this relationship further, the present study examined the inhibitory effect of selective alpha-1A [5-methylurapidil (5-MU) and nifedipine (NIF)] and alpha-1B [chloroethylclonidine (CEC)] antagonists on the pressor response to electrical stimulation (ES) of the spinal cord in pithed rats. Diastolic pressure changes were measured in the presence of 5-MU or CEC and compared with control responses. Pretreatment with 5-MU (0.5 mg/kg i.v.) significantly suppressed the ES pressor response (50-80% inhibition) at all stimulation frequencies. Likewise, NIF (inhibitor of calcium influx associated with alpha-1A adrenoceptor activation) selectively inhibited the pressor response to ES to the same degree as did 5-MU. CEC (25 mg/kg i.v.) also significantly shifted the ES response curve; however, this effect was mediated by activation of presynaptic alpha-2 receptors on sympathetic terminals because prior administration of idazoxan (5 mg/kg) prevented the inhibitory effect of CEC. Based on the potent inhibitory effects of 5-MU and NIF on the ES pressor response in the pithed rat, it was concluded that vascular alpha-1A adrenoceptors reside in the synaptic region of neurovascular junction where they are primarily activated by neuronal norepinephrine release.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明，在体内，全身动脉压受外周交感神经与血管α-1A肾上腺素能受体相互作用的紧张性调节。为了进一步探究这种关系，本研究检测了选择性α-1A拮抗剂[5-甲基尿嘧啶（5-MU）和硝苯地平（NIF）]以及α-1B拮抗剂[氯乙可乐定（CEC）]对脊髓电刺激（ES）引起的去大脑大鼠升压反应的抑制作用。在存在5-MU或CEC的情况下测量舒张压变化，并与对照反应进行比较。静脉注射5-MU（0.5 mg/kg）预处理在所有刺激频率下均显著抑制ES升压反应（抑制率为50-80%）。同样，NIF（与α-1A肾上腺素能受体激活相关的钙内流抑制剂）对ES升压反应的抑制程度与5-MU相同。静脉注射CEC（25 mg/kg）也显著改变了ES反应曲线；然而，这种作用是由交感神经末梢突触前α-2受体的激活介导的，因为预先给予咪唑克生（5 mg/kg）可阻止CEC的抑制作用。基于5-MU和NIF对去大脑大鼠ES升压反应的强效抑制作用，得出结论：血管α-1A肾上腺素能受体位于神经血管交界处的突触区域，主要由神经元去甲肾上腺素释放激活。（摘要截选至250字）
