Circulation, Vol 70, 908-916, Copyright © 1984 by American Heart Association
K Maekawa, CS Liang, A Tsui, BT Chen and S Kawashima
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.
ARTICLES
Vasodilative effect of hydralazine in awake dogs: the roles of prostaglandins and the sympathetic nervous system
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