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

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 290; no. 4; pp. H1617 - H1623
• Main Authors: Qamirani, Erion, Razavi, Habib M, Wu, Xin, Davis, Michael J, Kuo, Lih, Hein, Travis W
• Format: Journal Article
• Language: English
• Published: United States 01.04.2006
• Subjects: Animals; Arterioles - drug effects; Arterioles - physiology; Cells, Cultured; Coronary Vessels - drug effects; Coronary Vessels - physiology; Enzyme Activation - drug effects; Female; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Male; Myocytes, Smooth Muscle - drug effects; Myocytes, Smooth Muscle - physiology; Potassium Channels, Inwardly Rectifying - agonists; Potassium Channels, Inwardly Rectifying - physiology; Sodium Azide - administration & dosage; Sodium-Potassium-Exchanging ATPase - drug effects; Sodium-Potassium-Exchanging ATPase - physiology; Swine; Vasodilation - drug effects; Vasodilation - physiology; Vasodilator Agents - administration & dosage
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00746.2005

1 Department of Medical Physiology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, College Station, Texas; and 2 Department 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 (NaN 3 ), a potent vasodilator, causes severe hypotension on accidental exposure. Although NaN 3 has been shown to increase coronary blood flow, the direct effect of NaN 3 on coronary resistance vessels and the mechanism of the NaN 3 -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 cmH 2 O intraluminal pressure and dilated acutely, in a concentration-dependent manner, to NaN 3 (0.1 µM to 50 µM). The NaN 3 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, Ca 2+ -activated, and voltage-dependent K + channels affected NaN 3 -induced dilation. However, the vasomotor action of NaN 3 was significantly attenuated in a similar manner by the inward rectifier K + (K IR ) channel inhibitor Ba 2+ , the Na + -K + ATPase inhibitor ouabain, or the guanylyl cyclase inhibitor 1 H -[1,2,4]oxadiazolo[4,3,- a ]quinoxalin-1-one (ODQ). Ba 2+ , in combination with either ouabain or ODQ, nearly abolished the vasodilatory response. However, there was no additive inhibition by combining ouabain and ODQ. The NaN 3 -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, NaN 3 acutely enhanced Ba 2+ -sensitive K IR current in isolated coronary arteriolar smooth muscle cells. Collectively, this study demonstrates that NaN 3 , 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 Address for reprint requests and other correspondence: T. W. Hein, Dept. of Surgery, Scott & White Memorial Hospital, College of Medicine, The Texas A&M Univ. System Health Science Ctr., 702 Southwest H. K. Dodgen Loop, Temple, TX 76504 (e-mail: thein{at}tamu.edu )