Lundergan C F, Fitzpatrick T M, Rose J C, Ramwell P W, Kot P A
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, District of Columbia.
J Pharmacol Exp Ther. 1988 Jul;246(1):102-6.
Furosemide is a potent vasodilator of the systemic arterial and venous systems. The mechanism of vasodilatation, however, remains unclear. We investigated the vasodilatory effect of furosemide and its relation to endogenous prostaglandins (PGs). In the isolated canine lung lobe, furosemide significantly decreased mean pulmonary artery pressure. This effect was inhibited by indomethacin. Furosemide also attenuated the pulmonary vasoconstrictor response to the endoperoxide analog U46619 and PGF2 alpha. The pulmonary pressor response to a submaximal constrictor dose of arachidonic acid was significantly enhanced by furosemide, however, the pressor response to a maximal constrictor dose of arachidonic acid was attenuated, although not significantly. In animals pretreated with indomethacin, furosemide had no effect on the vascular response to PGF2 alpha, but the response to U46619 was significantly increased. Prostacyclin reduced pulmonary perfusion pressure and inhibited the pressor response to PGF2 alpha and U46619. Furosemide failed to alter inactivation of PGE2 on pulmonary lobe transit. We conclude that: 1) the vasodilatory activity of furosemide is mediated by increased production and not decreased metabolism of an endogenous cyclooxygenase product; 2) the effect of prostacyclin on vascular reactivity is similar to that of furosemide; and 3) local formation of prostacyclin by vascular tissue most likely mediates the vascular activity of furosemide.
呋塞米是一种强效的全身动脉和静脉系统血管扩张剂。然而，其血管扩张机制尚不清楚。我们研究了呋塞米的血管扩张作用及其与内源性前列腺素（PGs）的关系。在离体犬肺叶中，呋塞米显著降低平均肺动脉压。这种作用被吲哚美辛抑制。呋塞米还减弱了对过氧化物类似物U46619和前列腺素F2α的肺血管收缩反应。呋塞米使对亚最大收缩剂量花生四烯酸的肺升压反应显著增强，然而，对最大收缩剂量花生四烯酸的升压反应虽未显著减弱，但有所减弱。在用吲哚美辛预处理的动物中，呋塞米对血管对前列腺素F2α的反应无影响，但对U46619的反应显著增强。前列环素降低肺灌注压，并抑制对前列腺素F2α和U46619的升压反应。呋塞米未能改变肺叶转运过程中前列腺素E2的失活。我们得出以下结论：1）呋塞米的血管扩张活性是由内源性环氧化酶产物生成增加介导的，而非代谢减少；2）前列环素对血管反应性的影响与呋塞米相似；3）血管组织局部形成前列环素很可能介导了呋塞米的血管活性。
