Hardebo J E, Kåhrström J, Owman C
Department of Medical Cell Research, University of Lund, Sweden.
Q J Exp Physiol. 1989 Jul;74(4):475-91. doi: 10.1113/expphysiol.1989.sp003295.
The ability of electrical field stimulation in releasing transmitter from isolated blood vessels in vitro, during recordings of constrictor or dilator responses, is dependent upon an appropriate choice of stimulation parameters which avoid concomitant change in tone due to a direct effect on the vascular smooth muscle membrane. In many species, including man, small arteries such as pial arteries frequently respond to electrical field stimulation with a dilatation which is TTX-resistant. Such dilatations occur even with stimulus parameters of 7.5 V/60 mA at 0.1 ms, 6 Hz. The stimulation parameters required to induce the TTX-resistant response are just above those needed to obtain a purely neurogenic contractile or dilatory response in vessels equipped with a dense net of adrenergic nerves, such as rabbit central ear artery, and, in addition, highly sensitive postsynaptic alpha- or beta-adrenergic receptors, such as the buccal segment of the facial vein. This prompted us to characterize further the nature of the response. It was tested whether the relaxation, despite being TTX-resistant, might be neurogenic in origin. 4-Aminopyridine, in doses that usually enhance the transmitter release from nerves, did not affect the response. Blockade by a variety of dilator antagonists, the presence of excess amounts of known dilators or removal or emptying of known vasodilator nerves did not inhibit the response. Removal of extracellular calcium did not abolish the response. Therefore, it is highly unlikely that neuronal release is involved to any measurable extent in this response. The relaxation was not significantly affected by removal of endothelium, blockade of endothelium-derived relaxing factor, or interference with mast cells. At modest stimulatory parameters (12-13 V/96-104 mA at 0.1 ms, 7-8 V/56-64 mA at 0.3 ms, at 6 Hz) chlorine gas bubbles could be seen forming at the electrode or mounting hook; this gas is toxic to the musculature and relaxes a pre-contracted vessel. At stronger stimulation (greater than 12 V/96 mA, greater than 0.3 ms at 6 Hz) a relaxation supervened that was almost prevented by scavengers of oxygen free-radical metabolites. This relaxation was partly irreversible, indicating damage to the contractile elements. We conclude that when studying electrically induced release of vasodilator transmitters in vessels not equipped with an highly effective transmitter/receptor function, even a small rise in stimulatory parameters--in order to enhance transmitter release--causes relaxations that are non-neurogenic.(ABSTRACT TRUNCATED AT 400 WORDS)
在记录血管收缩或舒张反应的过程中，体外电场刺激从离体血管释放递质的能力，取决于对刺激参数的恰当选择，这些参数应避免因直接作用于血管平滑肌膜而导致张力的伴随性改变。在包括人类在内的许多物种中，诸如软脑膜动脉之类的小动脉对电场刺激常常产生一种对河豚毒素（TTX）不敏感的舒张反应。即便采用7.5伏/60毫安、0.1毫秒、6赫兹的刺激参数，这种舒张反应依然会出现。诱导这种对TTX不敏感反应所需的刺激参数，刚好高于在配备有密集肾上腺素能神经网的血管（如兔中耳动脉）中获得纯粹神经源性收缩或舒张反应所需的参数，此外，还高于在诸如面静脉颊段等具有高度敏感的突触后α或β肾上腺素能受体的血管中所需的参数。这促使我们进一步明确该反应的性质。我们测试了尽管这种舒张对TTX不敏感，但它在起源上是否可能是神经源性的。通常能增强神经递质释放的4 - 氨基吡啶剂量，并未影响该反应。多种舒张拮抗剂的阻断、已知舒张剂过量存在、已知血管舒张神经的去除或排空，均未抑制该反应。去除细胞外钙也未消除该反应。因此，极不可能在任何可测量的程度上涉及神经元释放参与此反应。去除内皮、阻断内皮源性舒张因子或干扰肥大细胞，对该舒张反应均无显著影响。在适度的刺激参数下（0.1毫秒、6赫兹时为12 - 13伏/96 - 104毫安，0.3毫秒时为7 - 8伏/56 - 64毫安），可看到电极或固定钩处形成氯气气泡；这种气体对肌肉组织有毒，并能使预先收缩的血管舒张。在更强的刺激下（大于12伏/96毫安，6赫兹时大于0.3毫秒），会出现一种舒张反应，自由基代谢产物清除剂几乎可完全阻止这种舒张。这种舒张部分是不可逆的，表明收缩成分受到了损伤。我们得出结论，在研究未配备高效递质/受体功能的血管中电诱导的血管舒张递质释放时，即使刺激参数有小幅升高——以增强递质释放——也会导致非神经源性的舒张。（摘要截选至400字）
