| Objective: To investigate the effects of Bisoprolol on resting tension of aged rats’ thoracic aorticrings, and the vascular pre-contraction of potassium chloride（KCl）, norepinephrine （NE） atdifferent pH, and to explore the underlying the possible mechanisms.Methods: The isolated vascular tension experimental method was applied. aged rats weredecapitated, removed the thoracic aorta by thoracotomy and placed it into physiological saltsolution （PSS） at 4°C. It was fixed at the both ends, carefully removed the surrounding adiposetissue, cut into vascular rings at the length of about 2 3 mm. The vascular ring was thwartshipshung with two stainless steel micro-hooks through the lumen and dipping in the bath canal, thebottom was fixed and the top was connected to the tension transducer, the changes in tension ofvascular rings were recorded by BL-420F computer bio-signal acquisition and analysis system.The bath contains the PSS of pH value was 7.4, temperature was 37°C , and infused with100%O2, and adjusted the underlying tension to 2.0 g, equilibrated for 1 h and then started theexperiment. Investigated the impacts of Bisoprolol in the PSS at pH value of 7.4,6.9,7.9 to NE(1×10-6mol/L), KCl （60 mmol/L） on induced-aged rats’ isolated thoracic aortic ring contraction,as well as the influences of nitric oxide synthase （NOS） inhibitor N-nitro-L-arginine methyl ester（L-NAME, 1×10-4 mol/L）, prostacyclin （PGI2） synthase inhibitionagent indomethacin (Indo, 1×10-5mol/L), KVchannel blocking agent 4-amino pyridine (4-AP, 1×10-3mol/L) of KATPchannelblocker glibenclamide(Gli, 1×10-5mol/ L), BKCachannel blocker tetraethylammonium (TEA,1×10-2mol/L), Kirchannel blocker Barium chloride (BaCl2, 1×10-3mol/L) at different pH valueson the role of Bisoprolol .Results: （1） There were no relaxant effect of various concentrations of bisoprolol (1×10-9to1×10-5mol/L) on the thoracic aortic rings in the resting state, compared with Saline controlgroup ,there were no（P> 0.05）.（2） There were concentration-dependent relaxant effects ofconcentrations of bisoprolol (1×10-9to 1×10-5)mol/Lon NE (1×10-6) mol/L precontracted aorticrings. Among of them, the PSS of pH value of 7.9, the EC50was （0.76±0.47）×10-7mol/L, theEmaxwas 88.00±4.1%. Compared to the Saline control group , there was statistically significantdifference（P <0.01）; PSS of pH value of 6.9, EC50was （1.03±0.25）×10-7mol/L, maximaldiastolic percentage （Emax）was 89.18±2.9%, compared to Saline control group, the differenceswere statistically significant （P <0.01）; PSS of pH value of 7.4, EC50was (1.09±0.91×10-6)mol/L, maximal diastolic percentage （Emax） was 68.60±11.23%, there was statisticallysignificant difference compared with Saline control group （P <0.01）.（3）Bisoprolol (1 x 10-9to1×10-5)mol/L did not produce significant changes in tensions of KCl （60mmol/L）-induced vasoconstriction, compared with the Saline control group, there was no statistically significantdifference（P > 0.05）.（4） After the NE (1×10-6mol/L)induced contraction reached the platform,the addition of L-NAME (1×10-4mol/L)led to the changes of vascular tension, the arrival ofplateau value again was followed by an addition of bisoprolol(the pH was 6.9 while theconcentration was 10-7mol/L, the pH was 7.9 and the concentration was 10-7mol/L, the pHwas7.4 while concentration was 10-6mol/L), the vasodilator effect of bisoprolol significantlyreduced, compared with the group without L-NAME, the difference was statistically significant（P <0.05）.（5） After the NE (1×10-6mol/L)induced contraction reached the platform, the additionof Indo (1×10-5mol/L) led to the changes of vascular tension, after the again arrival of plateauvalue, the addition of bisoprolol(the pH was 6.9 while the concentration was 10-7mol/L, the pHwas 7.9 and the concentration was 10-7mol/L, the pH was7.4 while concentration was 10-6mol/L), the vasodilator effect of bisoprolol significantly reduced, compared with the groupwithout Indo, the difference was statistically significant （P <0.01）.（6） After the NE (1×10-6mol/L)induced contraction reached the platform, the respective addition of TEA(1×10-2)mol/L,BaCl2(1×10-3)mol/L, Gli(1×10-5)mol/L led to the changes of vascular tension, after the againarrival of plateau value, the additions of bisoprolol(the pH was 6.9 while the concentration was10-7mol/L, the pH was 7.9 and the concentration was 10-7mol/L, the pH was7.4 whileconcentration was 10-6mol/L), the vasodilator effect of bisoprolol significantly reduced,compared to the group without TEA, the difference was statistically significant （P <0.01）. （7）After the NE (1×10-6mol/L)induced contraction reached the platform, the change of vasculartension followed the addition of 4-AP(1×10-3mol/L), after arrived the plateau value again, addedthe bisoprolol solution(the pH was 6.9 and the concentration was 10-7mol/L, the pH was 7.9 andthe concentration was 10-7mol/L, the pH was7.4 and concentration was 10-6mol/L), took theconstriction amplitude as 100%, the group without 4-AP was taken as control. In pH 6.9 , therewas no significant difference compared to control group（P > 0.05）. pH 7.9, pH 7.4 ,4-APinhibited the relaxation of the bisoprolol, there were statistically significant difference withcontrol group （P <0.01）.Conclusion：1. Bisoprolol produced no relaxation action in resting isolated aged rats’ thoracic aortic ring.2. Bisoprolol on NE (1×10-6mol / L) pre-contraction in aged rats’ isolated thoracic aortaperformed a concentration-dependent relaxant effect, and at pH 6.9 and 7.9, the diastolic effectof Bisoprololis was stronger than that of pH7.4.3. There was no obviously impact on the vascular tension of KCl （60 mmol / L） pre-contractedaged rats’ isolated thoracic aortic rings.4. In different pH values, the relaxation effect of bisoprolol on NE (1×10-6mol / L) pre-contraced aged rats’ isolated thoracic aorta rings counted on endothelium-dependent.5. In pH7.9, pH 7.4, the relaxation action of bisoprolol on aged rats’ isolated thoracic aortic ringsmay be generally related to the KATPchannel, KVchannel of BKCachannels and Kir channels.Meanwhile in pH 6.9, the KATPchannels, BKCachannels and Kir channels might be the relatedfactors. |
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