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Nitroglycerin-patch induced tolerance is associated with reduced ability of nitroglycerin to increase exhaled nitric oxide.
Agvald, Per; Hammar, Linus; Gustafsson, Lars E.
Afiliação
  • Agvald P; Division of Physiology, Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden. Per.Agvald@fyfa.ki.se
Vascul Pharmacol ; 43(6): 449-57, 2005 Dec.
Article em En | MEDLINE | ID: mdl-16230051
Nitroglycerin (GTN), used in the treatment of ischemic heart disease, acts through the liberation of nitric oxide (NO). However, its clinical use is limited due to tolerance development. Expired NO was used as an indicator of GTN-bioactivation and was measured together with plasma nitrite and mean arterial pressure (MAP) during GTN indicator infusions. The model was applied in rabbits subjected to various time periods of low-dose GTN pretreatment by patch application for 1, 24 and 72 h. Pretreatment with GTN-patch resulted in significant attenuation of expired NO from the GTN indicator infusion in the 24 h and 72 h pretreatment groups compared to placebo (72 h). Dose-response curves with increasing GTN infusions after 24 h GTN-patch pretreatment revealed a significant attenuation of the MAP decrease compared to placebo. GTN-induced changes in plasma nitrite correlated to increases in expired NO and decreases in MAP. This indicates that expired NO could serve as an indicator of NO generation from GTN in the vascular system. We conclude that GTN tolerance is associated with reduced capacity to generate NO from GTN. Care should be taken in using MAP-reduction to evaluate tolerance since high indicator doses could liberate sufficient amounts of NO to elicit maximal MAP decrease even in tolerant animals.
Assuntos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasodilatadores / Nitroglicerina / Óxido Nítrico Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Vascul Pharmacol Assunto da revista: ANGIOLOGIA / FARMACOLOGIA Ano de publicação: 2005 Tipo de documento: Article País de afiliação: Suécia País de publicação: Estados Unidos
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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vasodilatadores / Nitroglicerina / Óxido Nítrico Tipo de estudo: Risk_factors_studies Limite: Animals Idioma: En Revista: Vascul Pharmacol Assunto da revista: ANGIOLOGIA / FARMACOLOGIA Ano de publicação: 2005 Tipo de documento: Article País de afiliação: Suécia País de publicação: Estados Unidos