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This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/H1617    most recent 00746.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Qamirani, E. Articles by Hein, T. W. Search for Related Content PubMed PubMed Citation Articles by Qamirani, E. Articles by Hein, T. W.

Sodium azide dilates coronary arterioles via activation of inward rectifier K⁺ channels and Na⁺-K⁺-ATPase

¹Department of Medical Physiology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, College Station, Texas; and ²Department of Surgery, Scott & White Memorial Hospital, College of Medicine, The Texas A&M University System Health Science Center, Temple, Texas

Submitted 14 July 2005 ; accepted in final form 18 November 2005

Sodium azide (NaN₃), a potent vasodilator, causes severe hypotension on accidental exposure. Although NaN₃ has been shown to increase coronary blood flow, the direct effect of NaN₃ on coronary resistance vessels and the mechanism of the NaN₃-induced response remain to be established. To address these issues without confounding influences from systemic parameters, subepicardial coronary arterioles were isolated from porcine hearts for in vitro study. Arterioles developed basal tone at 60 cmH₂O intraluminal pressure and dilated acutely, in a concentration-dependent manner, to NaN₃ (0.1 µM to 50 µM). The NaN₃ response was not altered by the nitric oxide synthase inhibitor N^G-nitro-L-arginine methyl ester or endothelial removal. Neither inhibition of phosphoinositol 3-kinase and tyrosine kinases nor blockade of ATP-sensitive, Ca²⁺-activated, and voltage-dependent K⁺ channels affected NaN₃-induced dilation. However, the vasomotor action of NaN₃ was significantly attenuated in a similar manner by the inward rectifier K⁺ (K_IR) channel inhibitor Ba²⁺, the Na⁺-K⁺ ATPase inhibitor ouabain, or the guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Ba²⁺, in combination with either ouabain or ODQ, nearly abolished the vasodilatory response. However, there was no additive inhibition by combining ouabain and ODQ. The NaN₃-mediated vasodilation was also attenuated by morin, an inhibitor of phosphatidylinositolphosphate (PIP) kinase, which can regulate K_IR channel activity. With the use of whole cell patch-clamp methods, NaN₃ acutely enhanced Ba²⁺-sensitive K_IR current in isolated coronary arteriolar smooth muscle cells. Collectively, this study demonstrates that NaN₃, at clinically toxic concentrations, dilates coronary resistance vessels via activation of both K_IR channels and guanylyl cyclase/Na⁺-K⁺-ATPase in the vascular smooth muscle. The K_IR channels appear to be modulated by PIP kinase.

vasodilation; ion channel; physiology