Sodium azide dilates coronary arterioles via activation of inward rectifier K+ channels and Na+-K+-ATPase.
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 microM to 50 microM). 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 1H-[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.
Qamirani
Erion
E
Dept. of Medical Physiology, The Texas A&M University System Health Science Center, College Station, TX, USA.
Razavi
Habib M
HM
Wu
Xin
X
Davis
Michael J
MJ
Kuo
Lih
L
Hein
Travis W
TW
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000819:agonists / Q000502:physiology*; D019810:Sodium Azide / Q000008:administration & dosage*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000008:administration & dosage
D024661:Potassium Channels, Inwardly Rectifying; D014665:Vasodilator Agents; D019810:Sodium Azide; D000254:Sodium-Potassium-Exchanging ATPase