Cantley L G, Spokes K, Clark B, McMahon E G, Carter J, Epstein F H
Division of Nephrology, Beth Israel Hospital, Boston, Massachusetts.
Kidney Int. 1993 Dec;44(6):1217-23. doi: 10.1038/ki.1993.371.
Infusion of radiocontrast agents in vivo results in renal artery constriction and subsequent renal hypoperfusion. To examine the role of endothelin and of prostaglandins in radiocontrast-mediated renal vasoconstriction, rats were treated with an endothelin receptor antagonist, CP170687, and with indomethacin. The dose of CP170687 utilized was sufficient to reverse endothelin1-mediated constriction of isolated aortic rings and of renal blood flow in intact rats. In normal rats there was a transient drop in renal blood flow to 80% of baseline following sodium iothalamate injection, an effect which was not prevented by CP170687. In rats first given indomethacin, the drop in renal blood flow was more pronounced (to 63% of baseline) and was sustained. In this instance, CP170687 fully reversed the sustained decrease of renal perfusion. CP170687 also diminished the rise in systemic blood pressure seen following iothalamate injection. In the absence of indomethacin, iothalamate increased urinary prostaglandin E2 to a maximum of sevenfold above baseline values. In summary, injection of radiocontrast results in an immediate decrease in renal blood flow that is counteracted by an increase in renal prostaglandin formation. When prostaglandin synthesis is inhibited, prolonged endothelin-mediated renal vasoconstriction is observed that is reversed by an endothelin receptor antagonist.
体内注入放射性造影剂会导致肾动脉收缩以及随后的肾灌注不足。为了研究内皮素和前列腺素在放射性造影剂介导的肾血管收缩中的作用，对大鼠使用了内皮素受体拮抗剂CP170687和吲哚美辛进行治疗。所使用的CP170687剂量足以逆转内皮素-1介导的离体主动脉环收缩以及完整大鼠的肾血流量减少。在正常大鼠中，注射碘他拉酸钠后肾血流量短暂下降至基线的80%，CP170687并不能阻止这一效应。在预先给予吲哚美辛的大鼠中，肾血流量下降更为明显（降至基线的63%）且持续存在。在这种情况下，CP170687完全逆转了肾灌注的持续下降。CP170687还减轻了注射碘他拉酸钠后出现的全身血压升高。在未使用吲哚美辛的情况下，碘他拉酸钠使尿前列腺素E2增加至最高比基线值高7倍。总之，注射放射性造影剂会导致肾血流量立即减少，这会被肾前列腺素生成增加所抵消。当前列腺素合成受到抑制时，会观察到内皮素介导的肾血管收缩持续存在，而内皮素受体拮抗剂可使其逆转。
