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Hydralazine decreases sodium nitroprusside-induced rat aortic ring relaxation and increased cGMP production by rat aortic myocytes.

Abstract
Association of hydralazine with nitrova-sodilators has long been known to be beneficial in the vasodilator treatment of heart failure. We previously found that hydralazine appeared to reduce the increase in cGMP induced by sodium nitroprusside in cultured rat aortic myocytes. In order to further explore this seemingly paradoxical interaction, we extended our initial observations in rat aortic myocytes and also determined the influence of hydralazine on sodium nitroprusside-induced relaxation of rat aortic rings. Hydralazine produced a concentration-dependent inhibition of sodium nitroprusside stimulation of cGMP production and caused a rightward shift of concentration-relaxation curves in aortic rings. A possible mechanism of the hydralazine-nitroprusside interaction could be the interference with bioactivation of the nitro-vasodilator to release nitric oxide. Recent evidence indicates that vascular NADH oxidase, an enzyme known to be inhibited by hydralazine, could be involved in this process. Accordingly, hydralazine was found to inhibit NADH oxidase activity in rat aortic myocytes at concentrations similar to those reducing sodium nitroprusside responses. It was concluded that antagonism of sodium nitroprusside action by hydralazine could be a consequence of interference with bioactivation of the former, apparently through inhibition of vascular NADH oxidase.
AuthorsHoracio Vidrio, Pilar González-Romo, Ezequiel Alvarez, Carlos Alcaide, Francisco Orallo
JournalLife sciences (Life Sci) Vol. 77 Issue 24 Pg. 3105-16 (Oct 28 2005) ISSN: 0024-3205 [Print] Netherlands
PMID15985267 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Multienzyme Complexes
  • Vasodilator Agents
  • Nitroprusside
  • Hydralazine
  • Nitric Oxide
  • NADH oxidase
  • NADH, NADPH Oxidoreductases
  • Cyclic GMP
Topics
  • Animals
  • Aorta (cytology, drug effects, metabolism)
  • Cells, Cultured
  • Cyclic GMP (metabolism)
  • Endothelium, Vascular (cytology, drug effects, metabolism)
  • Hydralazine (chemistry, pharmacology)
  • Male
  • Multienzyme Complexes (antagonists & inhibitors, metabolism)
  • Muscle Relaxation (drug effects, physiology)
  • Myocytes, Cardiac (cytology, drug effects, metabolism)
  • NADH, NADPH Oxidoreductases (antagonists & inhibitors, metabolism)
  • Nitric Oxide (metabolism)
  • Nitroprusside (chemistry, pharmacology)
  • Rats
  • Rats, Wistar
  • Vasodilation (drug effects)
  • Vasodilator Agents (chemistry, pharmacology)

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