Document Detail

Attenuation of vascular relaxation after development of tachyphylaxis to peroxynitrite in vivo.
MedLine Citation:
PMID:  9683438     Owner:  NLM     Status:  MEDLINE    
Peroxynitrite, formed endogenously by the near diffusion-limited reaction of nitric oxide with superoxide anion, induces vascular relaxation. This effect is subject to rapid tachyphylaxis, suggesting that peroxynitrite may alter subsequent vasorelaxant responses. The present study examined the effects of peroxynitrite on mean arterial pressure and hindquarter, renal, and mesenteric vascular resistances in pentobarbital-anesthetized rats. Peroxynitrite induced dose-dependent decreases in mean arterial pressure and hindquarter and mesenteric vascular resistances. The repetitive administration of peroxynitrite resulted in the rapid development of tachyphylaxis, with subsequent doses producing progressively smaller effects. After the development of tachyphylaxis to peroxynitrite, the hemodynamic effects produced by the systemic administration of acetylcholine and prostacyclin were significantly attenuated, whereas the hemodynamic responses to bradykinin and the nitric oxide donor (Z)-1-¿N-methyl-N-[6(N-methylammoniohexyl)amino]¿diazen-1-++ +ium-1, 2-diolate (MAHMA NONOate) remained unchanged. These results demonstrate that 1) peroxynitrite is a potent vasorelaxant in vivo, 2) peroxynitrite-mediated vasodilatation is subject to the development of rapid tachyphylaxis, and 3) peroxynitrite alters the vascular smooth muscle response to prostacyclin, perhaps via inactivation of vascular smooth muscle ATP-sensitive potassium channel function.
N A Benkusky; S J Lewis; N W Kooy
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  275     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1998 Aug 
Date Detail:
Created Date:  1998-09-16     Completed Date:  1998-09-16     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  H501-8     Citation Subset:  IM    
Department of Anatomy, The University of Iowa, Iowa City, Iowa 52242, USA.
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MeSH Terms
Acetylcholine / pharmacology
Blood Pressure / drug effects
Bradykinin / pharmacology
Hemodynamics / drug effects*,  physiology
Hydrazines / pharmacology
Nitrates / toxicity*
Nitric Oxide / pharmacology
Oxidants / toxicity*
Rats, Sprague-Dawley
Regional Blood Flow / drug effects
Splanchnic Circulation / drug effects
Vascular Resistance / drug effects
Vasodilation / drug effects,  physiology*
Grant Support
Reg. No./Substance:
0/1-hexanamine-6-(2-hydroxy-1-methyl-2-nitrosohydrazine)-N-methyl; 0/Hydrazines; 0/Nitrates; 0/Oxidants; 10102-43-9/Nitric Oxide; 26404-66-0/peroxynitric acid; 51-84-3/Acetylcholine; 58-82-2/Bradykinin

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