Wallnöfer A, Weir S, Rüegg U, Cauvin C
Preclinical Research, Sandoz, Ltd., Basel, Switzerland.
J Cardiovasc Pharmacol. 1989;13 Suppl 5:S23-31; discussion S45. doi: 10.1097/00005344-198900135-00008.
The effects of endothelin-1 (ET-1) on tension and membrane potential in rat isolated mesenteric resistance vessels (MRVs) and on 45Ca influx, 45Ca efflux, inositol-1,4,5-triphosphate (IP3) production, and cytoplasmic Ca2+ concentration ([Ca2+]1) in cultured aortic smooth muscle cells were compared with those of other agonists. ET-1 induced contractions of the MRVs, which were slow in onset, but reached a similar maximum amplitude (at 10 nM ET-1) as that seen with norepinephrine (NE, 10 microM) or [arg8]vasopressin (AVP, 0.1 microM). The EC50 for ET-1 was 1.3 +/- 0.1 nM. Removal of extracellular Ca2+ reduced ET-1-induced contractions to 11 +/- 3% of those in Ca2+-containing medium. With NE, the same procedure reduced contractions to 47 +/- 7% of those in Ca2+-containing medium, while with AVP, the reduction was similar in magnitude to that induced by ET-1 (11 +/- 5% of those in Ca2+-containing medium). Relaxation of ET-1-induced and NE-induced contractions by diltiazem was not complete (maximal at 58 +/- 6% with 10 microM diltiazem after 6 nM ET-1, and at 70 +/- 3% after 0.1 microM NE), in contrast to that of 80 mM K+-induced contractions, which were potently (IC50 = 0.2 microM) and completely reversed (100% relaxation at 10 microM diltiazem). ET-1 (6 nM) caused a small but significant depolarization of the MRVs (approximately 7 mV), the magnitude of which was only about one-third of that induced by equieffective contractile concentrations of NE and AVP. The voltage-sensitive Ca2+ channel agonist Bay K 8644 (1 microM), in contrast to ET-1, NE, and AVP, produced a small contraction (30 +/- 2% of the maximum response to NE), but no further depolarization when added in the presence of 15 mM K+ (which elicited approximately 12 mV depolarization but no contraction).(ABSTRACT TRUNCATED AT 250 WORDS)
将内皮素 -1（ET -1）对大鼠离体肠系膜阻力血管（MRV）的张力和膜电位的影响，以及对培养的主动脉平滑肌细胞中45Ca内流、45Ca外流、肌醇 -1,4,5 -三磷酸（IP3）生成和细胞质Ca2 +浓度（[Ca2 +]i）的影响，与其他激动剂的影响进行了比较。ET -1引起MRV收缩，其起效缓慢，但达到的最大幅度（在10 nM ET -1时）与去甲肾上腺素（NE，10 microM）或[精氨酸8]血管加压素（AVP，0.1 microM）引起的相似。ET -1的EC50为1.3±0.1 nM。去除细胞外Ca2 +将ET -1诱导的收缩降低至含Ca2 +培养基中收缩的11±3％。对于NE，相同操作将收缩降低至含Ca2 +培养基中收缩的47±7％，而对于AVP，降低幅度与ET -1诱导的相似（含Ca2 +培养基中收缩的11±5％）。地尔硫卓对ET -1诱导的和NE诱导的收缩的松弛不完全（在6 nM ET -1后用10 microM地尔硫卓时最大为58±6％，在0.1 microM NE后为70±3％），与80 mM K +诱导的收缩相反，后者被有效（IC50 = 0.2 microM）且完全逆转（在10 microM地尔硫卓时100％松弛）。ET -1（6 nM）引起MRV轻微但显著的去极化（约7 mV），其幅度仅约为等效应收缩浓度的NE和AVP诱导的幅度的三分之一。与ET -1、NE和AVP相反，电压敏感Ca2 +通道激动剂Bay K 8644（1 microM）产生轻微收缩（NE最大反应的30±2％），但在15 mM K +存在下添加时不产生进一步的去极化（15 mM K +引起约12 mV去极化但无收缩）。（摘要截断于250字）
