Broad-range TRP channel inhibitors (2-APB, flufenamic acid, SKF-96365) affect differently contraction of resistance and conduit femoral arteries of rat
Abstract
Transient receptor potential (TRP) channels are proposed to contribute to membrane depolarization and Ca2+ influx into vascular smooth muscle (VSM) cells. Our aim was to study the effects of widely used broad-range TRP channel inhibitors - 2-aminoethoxydiphenyl borate (2-APB), flufenamic acid (FFA) and SKF-96365 - on the contraction of freshly isolated small and large arteries.
Endothelium-denuded resistance (approximate to 250 mu m) and conduit (approximate to 1000 mu m) femoral arteries were isolated from adult Wistar rats and mounted in wire myograph. The effects of the above mentioned TRP channel inhibitors and voltage-dependent calcium channel inhibitor nifedipine were studied on arterial contractions induced by phenylephrine, U-46619 or K+.
Phenylephrine-induced contractions were also studied in the absence of extracellular Na+ mRNA expression of particular canonical and melastatin TRP channel subunits in femoral vascular bed was determined. TRP channel inhibitors attenuated K+-induced contraction less than nifedipine.
Phenylephrine-induced contraction was more influenced by 2-APB in resistance arteries, while FFA completely prevented U-46619-induced contraction in both sizes of arteries. The absence of extracellular Na+ prevented the inhibitory effects of 2-APB, but not those of FFA.
The observed effects of broad-range TRP channel inhibitors, which were dependent on the size of the artery, confirmed the involvement of TRP channels in agonist-induced contractions. The inhibitory effects of 2-APB (but not those of FFA or SKF-96365) were dependent on the presence of extracellular Na+