Cardiovascular Effects of ω-Conopeptides in Conscious Rats: Mechanisms of Action
Cardiovascular Effects of ω-Conopeptides in Conscious Rats: Mechanisms of Action
复制标题
ω-Conopeptides 对清醒大鼠的心血管作用：作用机制
DOI：
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发表时间：
1992
期刊：
影响因子：
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通讯作者：
B. Hoffman
中科院分区：
文献类型：
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作者：
S. Bowersox;T. Singh;L. Nádasdi;Z. Żukowska;K. Valentino;B. Hoffman
总结：我们研究了一种新型神经元电压门控钙通道拮抗剂ω-芋螺肽对大鼠血流动力学反应的影响。静脉注射（i. v.）注射SNX-111（ω-芋螺肽MVIIA）剂量依赖性地降低清醒大鼠的动脉血压（BP）。脑室内（i. c. v.）SNX- 111注射（580 pmol）倾向于增加BP，在初始降低后，增加心率（HR）。清醒大鼠静脉注射SNX-111的剂量反应曲线呈双相。从亚降压剂量开始，SNX-111引起长时间阻断脊髓动物交感神经刺激引起的升压反应，但不能阻止外源性去甲肾上腺素（NE）引起的BP升高。用组胺拮抗剂预处理大鼠部分阻断了较高剂量（870和2，900 nmol/kg）SNX-111的肿胀作用。在位置10（[Ala 10]-MV 11 A）的精氨酸丙氨酸取代显着减弱组胺介导的降压反应的组成部分。总之，这些发现表明静脉内给予SNX-111通过阻断交感神经传递和肥大细胞脱粒的组合降低全身BP;后者的功能似乎依赖于SNX-111氨基酸序列的位置10的精氨酸残基
Summary: We examined the effects of ω-conopeptides, a novel class of neuronal voltage-gated calcium channel antagonists, on hemodynamic responses in rats. Intravenous (i.v.) injections of SNX-111 (ω-conopeptide MVIIA) dose-dependently decreased arterial blood pressure (BP) in conscious rats. Intracerebroventricular (i.c.v.) SNX- 111 injections (580 pmol) tended to increase BP and, after an initial decrease, to increase heart rate (HR). The doseresponse curve for SNX-111 administered i.v. in conscious rats was biphasic. Beginning at subdepressor doses, SNX-111 caused a long-lasting blockade of pressor responses elicited by sympathetic nerve stimulation in pithed animals but did not prevent increases in BP evoked by exogenously administered norepinephrine (NE). Pretreatment of rats with histamine antagonists partially blocked the hypotensive effects of the higher (870 and 2,900 nmol/kg) doses of SNX-111. Substitution of alanine for arginine at position 10 ([Ala10]-MV11A) markedly attenuated the histamine-mediated component of the vasodepressor response. Together, these findings indicate that SNX-111 administered i.v. decreases systemic BP by a combination of blockade of sympathetic neurotransmission and mast cell degranulation; the latter function appears to be dependent on the arginine residue in position 10 of the amino acid sequence of SNX-111