Effect Of Telmisartan On Vascular Responses Of Thoracic Aorta In Rats

Objective:To investigate the effects and the possible mechanism of telmisartan on isolated thoracic aorta rings pre-contracted by norepinphrine (NE) or potassium chloride (KC1).Methods:The rats were sacrificed by luxation and the thoracic aorta was quickly removed from each animal and placed in physiological salt solution (PSS). The aorta was carefully cleaned of adherent fat and connective tissue. The vessel was then cut into rings of about 2-3 mm in length. Two stainless-steel wires were passed through the lumen of each ring. One stirrup was connected to an isometric force transducer to measure tension in the vessels. The rings were placed in a 10ml organ chamber containing PSS. The rings were stretched until they exerted an optimal basal tension of 2g, and then were allowed to equilibrate for 1 hour with the bath fluid being changed every 15 minutes. The solution was bubbled with 100%O2. Rings of the isolated rat thoracic aorta were mounted in organ baths and isometric contractile force was measured. Isotonic tension of thoracic aortic rings precontracted by NE (1×10-6 mol/L) or KCl (60mmol/L) was recorded. The vasorelaxing action of telmisartan and effects of various drugs which include NG-nitro-L-arginine methyl ester (L-NAME, 1×10-4 mol/L), indomethacin (Indo, 1×10-5 mol/L), tetraethtylamine (TEA,1×10-2mol/L),BaCl2(1×10-3mol/L), glibenclamide (Gli,1×10-5mol/L) and 4-aminopyridine (4-AP,1×10-3mol/L)were observed in the rings. The effects of telmisartan on the extracellular Ca2+-dependent contraction and intracellular Ca2+-dependent contractions were also studied.Results:(1) Telmisartan (1×10-9-1×10-5 mol/L) had no effect on the resting tone (P>0.05). (2)Telmisartan (1×10-9-1×10-5mol/L) respectively concentration-dependently reduced the contraction induced by NE. The logECso of telmisartan respectively was-7.09±0.66.The Emax respectively was (26.57±4.29)%. (3) Telmisartan (1×10-9-1×10-5mol/L) had no effect on the contraction induced by KCl. (4) Telmisartan (1×10-9-1×10-5 mol/L) respectively concentration-dependently reduced the contraction of denude-endothlium aortic rings which induced by NE. There was significant difference between the rings with intact and denude endothelium (P<0.05). (4) On NE-induced precontraction, 1×10-9-1×10-5 mol/L telmisartan's vasodilation can be inhibited by TEA and BaCl2 (P<0.05). (5) On NE-induced precontraction, Gli, KB-R7943 and 4-AP can't inhibit telmisartan's vasorelaxant effects. (6) Telmisartan didn't attenuated contractions induced by adding NE and CaCl2 in the Ca2+-free medium.Conclusion:Telmisartan could produce remarkable vasodilatation on NE pre-contracted aorta rings in rats, while it didn't affect the resting tone. Its relaxation effect is via endothelium-dependent mechanisms and relevant to the production of NO. Telmisartan's vasodilatation on NE pre-contracted aorta rings in rats is probably via Kir channel and BKCa channel. KATP channel and KV channel is not involved. The relaxant mechanism of telmisartan may be unconcerned with the inhibition of extracellular Ca2+influx and intracellular Ca2+ release.