Eichler H G, Ford G A, Blaschke T F, Swislocki A, Hoffman B B
Department of Medicine, Stanford University School of Medicine, California 94305.
J Clin Invest. 1989 Jan;83(1):108-12. doi: 10.1172/JCI113845.
Patients with essential hypertension show an increase in vascular resistance. It is unclear whether this is caused by structural changes in the arterial wall or by hyperresponsiveness of vascular smooth muscle to endogenous alpha adrenergic agonists. Using the dorsal hand vein compliance technique we compared the changes in diameter of superficial veins in response to phenylephrine, an alpha 1 adrenergic receptor agonist, and to nitroglycerin, a venorelaxant, in patients with essential hypertension and in normotensive subjects. The dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) in the hypertensive subjects was 257 ng/min (geometric mean; log mean +/- SD was 2.41 +/- 0.54). In the control subjects the ED50 was 269 ng/min (geometric mean; log mean was 2.43 +/- 0.43). Maximal response (Emax) for phenylephrine was 84 +/- 13% in the hypertensive subjects and 90 +/- 6% in the control subjects. Differences in the group means of the ED50 (P = 0.92) or the Emax (P = 0.27) were not significant. There were no significant differences in the ED50 (P = 0.54) or the Emax (P = 0.08) for nitroglycerin between the two groups. These results show no evidence for a generalized change in alpha adrenergic responsiveness in hypertension and support the concept that increased blood pressure responses to alpha adrenergic stimulation in hypertensives are due to structural and geometric changes in the arterial wall rather than to an increased responsiveness of postsynaptic alpha adrenergic receptors. The phenylephrine studies were repeated in seven hypertensive patients during treatment with prazosin, an alpha 1 adrenergic antagonist. The mean dose ratio of the shift in phenylephrine ED50 (ED50 during prazosin therapy/ED50 before prazosin therapy) was 6.1. This indicates that small doses of prazosin (1-2 mg) cause significant in vivo shifts in the dose-response relationship of alpha adrenergic agonists. The dorsal hand vein compliance technique is useful in detecting systemic effects of alpha adrenergic antagonists.
原发性高血压患者表现出血管阻力增加。目前尚不清楚这是由动脉壁的结构变化还是血管平滑肌对内源性α肾上腺素能激动剂的高反应性引起的。我们使用手背静脉顺应性技术，比较了原发性高血压患者和血压正常受试者的浅表静脉直径对去氧肾上腺素（一种α1肾上腺素能受体激动剂）和硝酸甘油（一种静脉舒张剂）的反应变化。高血压受试者中产生50%最大静脉收缩的去氧肾上腺素剂量（ED50）为257 ng/min（几何平均数；对数平均数±标准差为2.41±0.54）。在对照受试者中，ED50为269 ng/min（几何平均数；对数平均数为2.43±0.43）。高血压受试者中去氧肾上腺素的最大反应（Emax）为84±13%，对照受试者中为90±6%。ED50（P = 0.92）或Emax（P = 0.27）的组均值差异不显著。两组之间硝酸甘油的ED50（P = 0.54）或Emax（P = 0.08）没有显著差异。这些结果表明，没有证据表明高血压患者的α肾上腺素能反应性发生了普遍变化，并支持这样一种观点，即高血压患者对α肾上腺素能刺激的血压反应增加是由于动脉壁的结构和几何变化，而不是由于突触后α肾上腺素能受体的反应性增加。在7名高血压患者使用α1肾上腺素能拮抗剂哌唑嗪治疗期间，重复进行了去氧肾上腺素研究。去氧肾上腺素ED50变化的平均剂量比（哌唑嗪治疗期间的ED50/哌唑嗪治疗前的ED50）为6.1。这表明小剂量的哌唑嗪（1 - 2 mg）会导致α肾上腺素能激动剂的剂量反应关系在体内发生显著变化。手背静脉顺应性技术有助于检测α肾上腺素能拮抗剂的全身效应。
