Ishii M, Uehara Y, Hirata Y, Atarashi K, Ikeda T, Sugimoto T, Takeda T, Murao S
Jpn Circ J. 1982 May;46(5):494-502. doi: 10.1253/jcj.46.494.
Altered prostacyclin metabolism may underlie essential hypertension. In this study, responses of plasma 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha: a stable metabolite of prostacyclin) to infused norepinephrine (NE) were compared in 14 normotensive subjects (NT) and 20 untreated patients with essential hypertension (EH). In addition, changes in systemic hemodynamics following NE-infusion were compared with changes in plasma 6-keto-PGF1 alpha. The subjects were all hospitalized and placed on a diet containing 6-8 g of salt per day. Blood pressure was recorded directly through the brachial artery, cardiac output (CO) was determined with the dye-dilution technique using cuvette and total peripheral vascular resistance (TPR) was calculated before and 60 min after NE-infusion. Arterial plasma 6-keto-PGF1 alpha was also determined before and after NE-infusion. The rate of NE-infusion was adjusted to elevate mean arterial pressure (MAP) by 10-15%. Plasma 6-keto-PGF1 alpha was radioimmunoassayed. Elevation of MAP was 13.0 +/- 1.2 (SE) in NTs and 11.7 +/- 1.4% in EHs. After NE-infusion, CO and TPR both significantly increased in NTs, while only CO increased significantly in EHs. Changes in CO and TPR were both significantly different between the two groups (p less than 0.01). Initial plasma 6-keto-PGF1 alpha was reduced in EHs as compared with NTs (174 +/- 15 vs 295 +/- 41 pg/ml, p less than 0.02). However, during NE-infusion, the increase in plasma 6-keto-PGF1 alpha was greater in EHs than in NTs (p less than 0.01). There was a significant negative correlation between changes in TPR and plasma PG (r = -0.36, p less than 0.05). The results indicate that responses of systemic hemodynamics and plasma 6-keto-PGF1 alpha to infused NE are different in the NT and EH groups, and that the absence of changes in TPR in EHs may be related to a marked increase in circulating prostacyclin. These findings, together with the reduced initial levels of plasma 6-keto-PGF1 alpha in EHs, probably represent altered prostacyclin metabolism in essential hypertension.
前列环素代谢改变可能是原发性高血压的潜在病因。在本研究中，比较了14名血压正常受试者（NT）和20名未经治疗的原发性高血压患者（EH）血浆6-酮-前列腺素F1α（6-酮-PGF1α：前列环素的稳定代谢产物）对输注去甲肾上腺素（NE）的反应。此外，将NE输注后全身血流动力学的变化与血浆6-酮-PGF1α的变化进行了比较。受试者均住院，每天食用含6 - 8克盐的饮食。通过肱动脉直接记录血压，使用比色皿通过染料稀释技术测定心输出量（CO），并在NE输注前和输注后60分钟计算总外周血管阻力（TPR）。在NE输注前后还测定了动脉血浆6-酮-PGF1α。将NE输注速率调整至使平均动脉压（MAP）升高10 - 15%。采用放射免疫分析法测定血浆6-酮-PGF1α。NT组MAP升高13.0±1.2（SE），EH组升高11.7±1.4%。NE输注后，NT组的CO和TPR均显著增加，而EH组仅CO显著增加。两组间CO和TPR的变化均有显著差异（p＜0.01）。与NT组相比，EH组初始血浆6-酮-PGF1α降低（174±15对295±41 pg/ml，p＜0.02）。然而，在NE输注期间，EH组血浆6-酮-PGF1α的增加幅度大于NT组（p＜0.01）。TPR变化与血浆PG之间存在显著负相关（r = -0.36，p＜0.05）。结果表明，NT组和EH组全身血流动力学及血浆6-酮-PGF1α对输注NE的反应不同，EH组TPR无变化可能与循环前列环素显著增加有关。这些发现，连同EH组血浆6-酮-PGF1α初始水平降低，可能代表原发性高血压中前列环素代谢改变。
