Isla M, Dyer D C
Department of Veterinary Physiology and Pharmacology, College of Veterinary Medicine, Iowa State University, Ames 50011.
Am J Obstet Gynecol. 1990 Oct;163(4 Pt 1):1337-44. doi: 10.1016/0002-9378(90)90716-k.
The differential inhibitory effect of the vasodilators on contractile responses to norepinephrine, serotonin, and potassium on isolated uterine artery ring segments from pregnant ewes within 2 weeks of term was quantified and correlated with the source of Ca++ for the vasoconstrictors producing the smooth muscle contraction. The contraction evoked by the vasoconstrictors was dependent on extracellular Ca++ and in agonist-induced contractions also on an intracellular pool of Ca++. Nifedipine effectively inhibited K(+)-induced (90 mmol/L) contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.95 +/- 0.9 x 10(-8) mol/L), whereas it was relatively ineffective in blocking norepinephrine-induced (10(-5) mol/L) or serotonin-induced (10(-5) mol/L) vasoconstriction (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 1.38 +/- 0.4 x 10(-4) mol/L and 2.04 +/- 0.4 x 10(-5) mol/L, respectively). Methoxyverapamil (D-600) strongly inhibited serotonin-induced contractions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 3.3 +/- 0.3 x 10(-7) mol/L). The phasic rather than the tonic components of the serotonin- and norepinephrine-induced contractions were more effectively inhibited by D-600 (p less than 0.05). Sodium nitroprusside preferentially blocked (p less than 0.05) the sustained tonic components of norepinephrine- and serotonin-induced vasoconstrictions (antagonist concentration to reduce the maximum contractile effect to the agonist to 50%, 7.1 +/- 0.4 x 10(-7) mol/L and 8.2 +/- 0.6 x 10(-7) mol/L, respectively). On the basis of these findings it is concluded that D-600 and sodium nitroprusside are more effective than nifedipine in blocking contractile responses due to receptor stimulation, and therefore might be more effective in the treatment of hypertensive emergencies in which these amines might be implicated.
对妊娠晚期2周内的怀孕母羊离体子宫动脉环段，研究了血管扩张剂对去甲肾上腺素、5-羟色胺和钾引起的收缩反应的差异抑制作用，并将其与引起平滑肌收缩的血管收缩剂的钙离子来源相关联。血管收缩剂引起的收缩依赖于细胞外钙离子，激动剂诱导的收缩还依赖于细胞内钙离子池。硝苯地平有效抑制钾（90 mmol/L）诱导的收缩（使激动剂最大收缩效应降低50%的拮抗剂浓度为1.95±0.9×10⁻⁸ mol/L），而在阻断去甲肾上腺素（10⁻⁵ mol/L）或5-羟色胺（10⁻⁵ mol/L）诱导的血管收缩方面相对无效（使激动剂最大收缩效应降低50%的拮抗剂浓度分别为1.38±0.4×10⁻⁴ mol/L和2.04±0.4×10⁻⁵ mol/L）。甲氧基维拉帕米（D-600）强烈抑制5-羟色胺诱导的收缩（使激动剂最大收缩效应降低50%的拮抗剂浓度为3.3±0.3×10⁻⁷ mol/L）。D-600更有效地抑制了5-羟色胺和去甲肾上腺素诱导收缩的相性成分而非紧张性成分（p＜0.05）。硝普钠优先阻断（p＜0.05）去甲肾上腺素和5-羟色胺诱导血管收缩的持续性紧张性成分（使激动剂最大收缩效应降低50%的拮抗剂浓度分别为7.1±0.4×10⁻⁷ mol/L和8.2±0.6×10⁻⁷ mol/L）。基于这些发现，得出结论：D-600和硝普钠在阻断受体刺激引起的收缩反应方面比硝苯地平更有效，因此在治疗可能涉及这些胺类的高血压急症中可能更有效。
