title: 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 (≈250 µm) and conduit (≈1000 µm) 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+.
authors.affiliation: Department of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic. Electronic address: michalbencze@gmail.com.
authors.forename: Michal
authors.initials: M
authors.lastname: Bencze
authors.affiliation: Department of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Michal
authors.initials: M
authors.lastname: Behuliak
authors.affiliation: Department of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic; Department of Physiology, Faculty of Science, Charles University, Prague, Czech Republic.
authors.forename: Anna
authors.initials: A
authors.lastname: Vavřínová
authors.affiliation: Department of Experimental Hypertension, Institute of Physiology, Czech Academy of Sciences, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Zicha
mesh_terms: D000818:Animals; D001896:Boron Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects* / Q000502:physiology; D005439:Flufenamic Acid / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D050051:Transient Receptor Potential Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D001896:Boron Compounds; D007093:Imidazoles; D050051:Transient Receptor Potential Channels; D005439:Flufenamic Acid; C109986:2-aminoethoxydiphenyl borate; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole
keywords: 2-APB; Femoral artery; Flufenamic acid; SKF-96365; TRP channel; Vascular contraction