Vasodilative effect of hydralazine in awake dogs: the roles of prostaglandins and the sympathetic nervous system.
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.