Uehara Y, Ishimitsu T, Kawabata Y, Matsuoka H, Ishii M, Sugimoto T
Second Department of Medicine, University of Tokyo, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1992 Jun;46(2):99-104. doi: 10.1016/0952-3278(92)90215-5.
To define the role of the renal eicosanoid system in sustaining renal homeostasis in hypertension, we investigated the alterations in urinary excretions of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), a stable metabolite of vasodepressor prostacyclin, and thromboxane B2 (TXB2), a stable metabolite of vasoconstrictor TXA2, when norepinephrine was continuously infused for 90 min in hypertensive (n = 13) and normotensive subjects (n = 14). There was no difference in plasma norepinephrine concentration after the infusion between the hypertensive and the normotensive subjects. Moreover, the percent changes in renal vascular resistance elicited by norepinephrine in the hypertensives were equal to those of the normotensive subjects. In the normotensive subjects, the norepinephrine infusion significantly increased urinary 6-keto-PGF1 alpha excretion and decreased urinary excretion of TX, both of which are beneficial for sustaining renal function. In fact, the greater the production of renal 6-keto-PGF1 alpha was, the less the reduction of renal blood flow and urinary sodium excretion was. In the hypertensive subjects, however, these normal responses of the renal eicosanoid system, seen in the normotensives, were abolished; urinary 6-keto-PGF1 alpha was unaltered and thromboxane generation was rather increased. Thus, the renal eicosanoid system dysfunctions in hypertensive subjects when the renal circulation is challenged by norepinephrine. These abnormal responses are likely to cause sodium retention and could contribute, in part, to the hypertensive mechanism in patients with essential hypertension.
为了确定肾脏类花生酸系统在维持高血压患者肾脏内环境稳定中的作用，我们研究了在高血压患者（n = 13）和正常血压受试者（n = 14）中持续输注去甲肾上腺素90分钟时，血管舒张剂前列环素的稳定代谢产物6-酮-前列腺素F1α（6-keto-PGF1α）和血管收缩剂血栓素A2的稳定代谢产物血栓素B2（TXB2）的尿排泄变化。输注后高血压患者和正常血压受试者的血浆去甲肾上腺素浓度没有差异。此外，去甲肾上腺素引起的高血压患者肾血管阻力的变化百分比与正常血压受试者相同。在正常血压受试者中，输注去甲肾上腺素显著增加了尿6-酮-PGF1α排泄，并减少了TX的尿排泄，这两者都有利于维持肾功能。事实上，肾脏6-酮-PGF1α的产生越多，肾血流量和尿钠排泄的减少就越少。然而，在高血压患者中，正常血压受试者中所见的肾脏类花生酸系统的这些正常反应被消除；尿6-酮-PGF1α未改变，血栓素生成反而增加。因此，当肾循环受到去甲肾上腺素挑战时，高血压患者的肾脏类花生酸系统功能失调。这些异常反应可能导致钠潴留，并可能部分促成原发性高血压患者的高血压机制。
