Maekawa K, Liang C S, Tsui A, Chen B T, Kawashima S
Circulation. 1984 Nov;70(5):908-16. doi: 10.1161/01.cir.70.5.908.
The relative roles of prostaglandins and the sympathetic nervous system in mediating the hypotensive effects of hydralazine were studied in awake dogs with and without pretreatment with indomethacin, propranolol, and phentolamine. In normal dogs, mean aortic pressure decreased 23 +/- 4 mm Hg after administration of hydralazine (cumulative dose of 0.8 mg/kg). This hypotensive effect of hydralazine was potentiated by phentolamine but was abolished by propranolol. Indomethacin caused a paradoxic pressor response (11 +/- 3 mm Hg) to hydralazine, which also was abolished by addition of phentolamine. Hydralazine produced vasodilation in the coronary, skeletal muscle (quadriceps), splanchnic, and renal circulations in normal dogs. The increase in coronary blood flow was associated with increased cardiac oxygen consumption and narrowed arteriovenous oxygen difference across the heart. Propranolol reduced the increases in cardiac oxygen consumption and coronary blood flow, but only indomethacin abolished the narrowed arteriovenous oxygen difference, suggesting that the increase in coronary blood flow was related to both the increased cardiac oxygen demand and prostaglandin-mediated active coronary vasodilation. The decrease in skeletal muscle vascular resistance after hydralazine was abolished by propranolol. Skeletal muscle vascular resistance actually increased after administration of hydralazine in dogs pretreated with both propranolol and indomethacin. These effects were blocked by the addition of phentolamine. Unlike the normal response, renal and splanchnic vascular resistances increased after administration of hydralazine in dogs pretreated with indomethacin. The splanchnic vasoconstriction was abolished by phentolamine, but the renal vascular change was affected by neither phentolamine nor propranolol. The results indicate that hydralazine does not produce uniform vasodilation in all organs and that the cardiovascular actions of hydralazine involve both prostaglandins and the sympathetic nervous system.
在清醒犬中，研究了前列腺素和交感神经系统在介导肼屈嗪降压作用中的相对作用，这些犬分为用或不用吲哚美辛、普萘洛尔和酚妥拉明预处理两组。在正常犬中，给予肼屈嗪（累积剂量0.8mg/kg）后，平均主动脉压下降23±4mmHg。酚妥拉明可增强肼屈嗪的这种降压作用，但普萘洛尔可消除该作用。吲哚美辛可使犬对肼屈嗪产生反常的升压反应（11±3mmHg），加入酚妥拉明后该反应也被消除。肼屈嗪可使正常犬的冠状动脉、骨骼肌（股四头肌）、内脏和肾循环血管舒张。冠状动脉血流量增加与心脏耗氧量增加及心脏动静脉氧差缩小有关。普萘洛尔可减少心脏耗氧量和冠状动脉血流量的增加，但只有吲哚美辛可消除动静脉氧差缩小，提示冠状动脉血流量增加与心脏氧需求增加和前列腺素介导的冠状动脉主动舒张均有关。肼屈嗪引起的骨骼肌血管阻力下降被普萘洛尔消除。在同时用普萘洛尔和吲哚美辛预处理的犬中，给予肼屈嗪后骨骼肌血管阻力实际上增加。加入酚妥拉明可阻断这些作用。与正常反应不同，在吲哚美辛预处理的犬中，给予肼屈嗪后肾和内脏血管阻力增加。酚妥拉明可消除内脏血管收缩，但肾血管变化不受酚妥拉明和普萘洛尔影响。结果表明，肼屈嗪并非在所有器官均产生一致的血管舒张作用，且肼屈嗪的心血管作用涉及前列腺素和交感神经系统。
