Callow I D, Campisi P, Lambert M L, Feng Q, Arnold J M
University of Western Ontario, London, Ontario, Canada N6A 5C1.
Am J Physiol. 1998 Sep;275(3):H837-43. doi: 10.1152/ajpheart.1998.275.3.H837.
Vasodilator prostaglandins are released in vitro from endothelium during adrenergic stimulation. We hypothesized that indomethacin would block this production in vivo and increase venoconstriction to alpha1- and alpha2-stimulation but not to the nonadrenergic agonist PGF2alpha. Hand vein distension was measured in 24 normal subjects (23.0 +/- 0.5 yr) during local infusions of phenylephrine (8-12,000 ng/min), clonidine (3-7,000 ng/min), or PGF2alpha (1-2,048 ng/min) plus indomethacin (3 microg/min) versus saline on two separate days. Dose-dependent venoconstriction to phenylephrine occurred in all subjects, with a parallel shift to the left with indomethacin (P = 0. 003) and a decrease in the phenylephrine 50% effective dose (1,009 vs. 241 ng/min, geometric means, P = 0.012). Venoconstriction to clonidine was more variable, with most subjects eliciting a biphasic response (initial venoconstriction followed by attenuation). With indomethacin, the dose-response curve was displaced up and to the left (P = 0.005), and peak venoconstriction was increased (51.1 +/- 6.8 vs. 27.2 +/- 5.3% of control, P = 0.018) without a biphasic response. In all subjects, PGF2alpha elicited dose-dependent venoconstriction that was not altered by indomethacin. Thus venous alpha1- and alpha2-stimulation results in release of vasodilator prostaglandins that antagonize the venoconstrictor response. This modulates the sympathetic response of venous smooth muscle and may be important in diseases with endothelial dysfunction.
在肾上腺素能刺激期间，血管舒张性前列腺素可在体外从内皮细胞释放。我们推测吲哚美辛会在体内阻断这种生成，并增强对α1和α2刺激的静脉收缩，但对非肾上腺素能激动剂前列腺素F2α则无此作用。在24名正常受试者（23.0±0.5岁）中，于两个不同日期分别局部输注去氧肾上腺素（8 - 12,000 ng/分钟）、可乐定（3 - 7,000 ng/分钟）或前列腺素F2α（1 - 2,048 ng/分钟）加吲哚美辛（3 μg/分钟）与生理盐水时，测量手部静脉扩张情况。所有受试者对去氧肾上腺素均出现剂量依赖性静脉收缩，使用吲哚美辛后曲线向左平行移动（P = 0.003），且去氧肾上腺素的50%有效剂量降低（几何均值分别为1,009与241 ng/分钟，P = 0.012）。对可乐定的静脉收缩反应更具变异性，大多数受试者出现双相反应（初始静脉收缩后接着减弱）。使用吲哚美辛后，剂量反应曲线向上并向左移位（P = 0.005），且静脉收缩峰值增加（分别为对照的51.1±6.8%与27.2±5.3%，P = 0.018），且无双相反应。在所有受试者中，前列腺素F2α引起剂量依赖性静脉收缩，且不受吲哚美辛影响。因此，静脉α1和α2刺激导致血管舒张性前列腺素释放，拮抗静脉收缩反应。这调节了静脉平滑肌的交感反应，在伴有内皮功能障碍的疾病中可能很重要。
