Cyclic nucleotide-gated channels contribute to thromboxane A2-induced contraction of rat small mesenteric arteries.
BACKGROUND
Thromboxane A(2) (TxA(2))-induced smooth muscle contraction has been implicated in cardiovascular, renal and respiratory diseases. This contraction can be partly attributed to TxA(2)-induced Ca(2+) influx, which resulted in vascular contraction via Ca(2+)-calmodulin-MLCK pathway. This study aims to identify the channels that mediate TxA(2)-induced Ca(2+) influx in vascular smooth muscle cells.


RESULTS
Application of U-46619, a thromboxane A(2) mimic, resulted in a constriction in endothelium-denuded small mesenteric artery segments. The constriction relies on the presence of extracellular Ca(2+), because removal of extracellular Ca(2+) abolished the constriction. This constriction was partially inhibited by an L-type Ca(2+) channel inhibitor nifedipine (0.5-1 microM). The remaining component was inhibited by L-cis-diltiazem, a selective inhibitor for CNG channels, in a dose-dependent manner. Another CNG channel blocker LY83583 [6-(phenylamino)-5,8-quinolinedione] had similar effect. In the primary cultured smooth muscle cells derived from rat aorta, application of U46619 (100 nM) induced a rise in cytosolic Ca(2+) ([Ca(2+)](i)), which was inhibited by L-cis-diltiazem. Immunoblot experiments confirmed the presence of CNGA2 protein in vascular smooth muscle cells.


CONCLUSIONS
These data suggest a functional role of CNG channels in U-46619-induced Ca(2+) influx and contraction of smooth muscle cells.
Leung
Yuk Ki
YK
Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Hong Kong, China.
Du
Juan
J
Huang
Yu
Y
Yao
Xiaoqiang
X
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D006152:Cyclic GMP / Q000494:pharmacology*; D007473:Ion Channels / Q000502:physiology*; D008638:Mesenteric Arteries / Q000187:drug effects*; D051381:Rats; D013928:Thromboxane A2 / Q000494:pharmacology*
D007473:Ion Channels; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000242:Cyclic AMP; D006152:Cyclic GMP