Effect Of Indobufen On Vascular Tone Of Isolated Thoracic Aortic Rings In Rats

Objective The study was designed to observe the effects and the possible mechanism of indobufen on the vasodilation in rat isolated aorta and to get an insight into its mechanism.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 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 hours 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 pre-contracted by potassium chloride (KCl,30mmol/L) or norepinephrine (NE,1×10-6 mol/L)was recorded. The response action of indobufen and effect of various drugs were observed in the rings.Results:(1) Indobufen (3×10-7～3×10-5mol/L) had no effect on the resting tone. (2) Indobufen concentration-dependently vasodilated the thoracic aortic rings precontracted by potassium chloride(KCl,30 mmol/L); the maximal vasodilation by 3×10-5 mol/L indobufen was (56.25×3.98)%, LogEC50=5.48±0.45. (3) Indobufen (3×10-7～3×10-5 mol/L) produced concentration-dependent vasodilation of rat isolated aortic rings pre-contracted by norepinephrine (NE,1×10-6 mol/L); the maximal relaxation rate was (65.04±2.66)%, LogEC50 =5.20±0.39. (4) Indobufen (3×10-7～3×100mol/L) concentration-dependently reduced the contraction of denude-endothlium thoracic aortic rings which induced by KCl or NE. There was respectively significant difference between the rings with intact and denude endothelium (P＜0.05). (5) On KCl-induced pre-contraction,3×10-7～3×10-5 mol/L Indobufen's vasodilation can be inhibited by TEA(P<0.01),4-AP(P<0.01), Gli (P<0.01) or BaCl2(P<0.01). (6) On KCl-induced pre-contraction, KB-R7943(1×10-6 mol/L) can significantly enhance the vasorelaxation induced by indobufen (P＜0.05); the maximal relaxation rate was(80.82±2.50)%, LogEC50=5.81±0.50. (7) On KCl-induced precontraction, Indobufen's relaxation was depressed by L-NAME(P<0.01), the blend of L-NAME and L-Arg (P＜0.05). (8) On NE pre-contracted rat thoracic aortic rings, TEA,4-AP or Gli, can block the vasodilatation induced by indobufen.Conclusion:(1) Indobufen did not affect the resting tone of rat thoracic aortic rings. (2) Indobufen could produce remarkable vasodilatation on KCl or NE pre-contracted rat isolated aortic rings. Its relaxtion effect is via endothelium-dependent mechanisms and relevant to the production of NO. (3) The relaxant mechanism of Indobufen may be concerned with BKCa channel, KV chnnel, Kir channel and KATP channel. (3) Indubufen produces a concentration-dependent vasorelaxation which can enhance by KB-R7943 (sodium calcium exchanger inhibiter).