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Adenosine is an endogenous in vivo quenched and widely distributed in the nervous system, cardiovascular system, digestive system and respiratory tissue, cell growth, differentiation, death and other activities of the physiological regulation substances. Showed a low level of sustained release of adenosine in the physiological state. Different adenosine receptor binding extracellular adenosine through the cell membrane, play a variety of biological roles. It has been confirmed in the vascular smooth muscle cell membrane A 1 , the A 2a , A 2b and A 3 four kinds Adenosine receptors belong to the G protein-coupled receptor superfamily, which A 1 and A 3 receptor Gi / Go-coupled receptors, A 2a and A 2b is Gs coupled receptors [1-3]. Under normal circumstances, the extracellular adenosine concentration is maintained in the 40 nmol / L 4 00nmol / L,. When ischemia and hypoxia occurs, on the one hand, the body's glucose and glycogen accelerating decomposition to generate ATP in order to supply the energy needs, ATP release energy to continue after degradation, and thus dramatically increase of intracellular cAMP level, and to release it to the cells outside to play its regulatory role; nerve cells, on the other hand, will quickly generate and release large amounts of adenosine and adenosine concentrations higher than normal 100-1000 times [4] . This massive release of adenosine under hypoxic conditions, is a very important regulator of vascular tone, can significantly affect vascular function, thereby affecting blood flow [5]. When the higher organism COD oxygen partial pressure is reduced, adenosine, the role of the vascular system is particularly significant. Our previous studies found that in normoxic conditions, adenosine able concentration-dependent relaxation of isolated rat basilar artery endothelium-dependent in this role, by activation of vascular smooth muscle on adenosine A of 2a receptor binding produced vasodilating effect. Adenosine can inhibit wow Pakistan due to rat basilar artery diastolic, and its dose-response curve to the right. Adenosine can significantly reduce the Na / K pump (Na / K -ATP enzyme) high and low affinity α subunit wow bar because of the affinity, suggesting that both participate in adenosine diastolic wow Palestinian induced basilar artery contraction reaction. Na / K pump is widely distributed in a variety of eukaryotic cell membranes of cells, including vascular smooth muscle cells. Found the NaK pump α subunits α1, α2, α3 and α4 four subtypes. When the Na / K pump is suppressed, may be due to increased intracellular sodium ion concentration and an increase in intracellular calcium, thus increasing vascular contraction. However, the Na / K pump mechanism of action has not been studied in the vasodilatory effect of adenosine clear literature wow Pakistan due to (10 -4 mol / L) can be partially blocking adenosine diastolic rats aortic role, that of Na / K pump to play a crucial role in the vasodilatory effect of adenosine. Our previous studies have confirmed that wow Pakistan due to a concentration-dependent contraction of the basilar artery, dose-response relationships rat basilar artery there are high and low affinity for two different functions of the sodium pump curve fitting results show, and the first time that adenosine diastolic wow Pakistan due to the contraction of rat basilar artery, wow bar because of the curve to the right of the dose-effect relationship, while significantly reducing the high-and low-affinity α-subunit on wow bar because of the affinity, suggesting, low-affinity Na / K The pumps are involved in adenosine diastolic wow Palestinian basilar artery contraction induced reaction. But the role of high affinity for the pump lower affinity pump 100 times greater, suggesting a high affinity sodium pump involved in the of adenosine relaxation of 5-HT vasoconstrictor effect. 5 - hydroxytryptamine (serotonin ,5-HT) is an inhibitory neurotransmitter. 5 - HT was first found in the serum, also known as serum hormone, widely present in mammalian tissues, high content in the cerebral cortex qualitative and synapses in the peripheral tissues, 5 - serotonin is a potent vascular and smooth muscle contraction agent. 5 - serotonin intense vasoconstriction is considered to be the main reason causing cerebral vasospasm and impaired blood flow. Our previous study also found, ouabain, can significantly enhance the 5-HT-induced hypertension in rat basal contraction effect, so that the 5-HT dose-response curve to the left prompt of Na / K pump to participate in the 5-HT induced hypertensive rat basilar artery the contraction. Basilar artery in rats hypoxic conditions of adenosine diastolic 5-HT-induced contractile response to what effect? ??Paper studies hypoxia, adenosine 5-HT inhibition of contraction of rat basilar artery, and to further explore in the case of oxygen Na / K pump is involved in the role of adenosine diastolic blood vessels. Objective: To investigate the relationship adenosine under hypoxic conditions 5 - due to serotonin regulation away from the rat basilar artery contraction and Na / K pump. Methods: The rats were decapitated immediately brain tissue together, together with the cerebral artery removed, soak in cold (4 ° C) of the PSS nutrient solution (concentration mmol / L: KCl 4.7, of NaCl 118.99, EDTA 0.027 Glucose 5.5 MgSO 4 .7 H 2 O 1.17, KH 2 PO 4 1.18, NaHCO 3 25). Removal of pia isolated basilar artery (basilar artery, BA), the clip 2mm arterial rings around, two having a diameter of 40μm tungsten wire penetrates the ring cavity, the fixed vascular ring Multi Myograph System-610M bath for can tentacles, continuing through to 95% O2 5% CO 2 gas mixture. Experimental hypoxic conditions continued to pass 95% N2 5% CO 2 gas mixture. Bath 37 ± 0.5 ℃ temperature is kept constant vascular standardized software. The tension transducer system changes in vascular tone by Myograph recorded on the computer. Observe the influence of drugs of its tension, and record changes in tension. Results: 1 5-HT from the body of the basilar artery ring concentration-dependent contraction effect on rats containing 5-HT concentrations were 10 -9 mol / L, 3 × 10 -9 , 10 -8 mol / L, 3 × 10 -8 mol / L, 10 -7 mol / L, 3 × 10 -7 mol / L, 10 -6 mol / L, 3 × 10 -6 mol / L, followed by perfusion of blood vessels, causing rats away from the body of the contraction of the basilar artery ring contraction force (mN): 0.03 ± 0.02,0.07 ± 0.03,0.19 ± 0.12,0.47 ± 0.21,1.87 ± 0.56,3.37 ± 0.61,4.86 ± 0.63,4.92 ± 0.63. Select 5 × 10 -7 mol / L (EC80) for a fixed drug concentration. Hypoxia induced rat basilar artery contraction effect of 5-HT at the the normoxia status 5 × 10 -7 mol / L 5-HT induced vascular contraction force rat isolated basilar artery ring hypoxia 40min, 80min, and 120min after vascular contraction amplitude percentage were: ± 17.85,112.79 ± 12.55, 101.30 ± 11.75,107.13 100%. Hypoxia 120min can enhance the reactivity of the basilar artery to 5-HT. Choose 40min as this experiment hypoxia time. 3 hypoxia on the vascular effects of adenosine diastolic rat basilar artery perfusion 10-3 mol / L adenosine 5-HT contraction of vascular relaxation rate of 100%, normoxia 10 -8 mol / L, 10 -7 mol / L, 10 -6 mol / L, 10 -5 mol / L, 10 -4 mol / L and 10 -3 mol / L adenosine 5-HT contraction basal artery diastolic percentage of 3.33 ± 4.22,11.42 ± 8.15,24.45 ± 14.83 49.85 ± 9.97,94.57 ± 9.48 and 100 ± 9.92; the hypoxia group 10 -8 mol / L, 10 -7 mol / L, 10 -6 mol / L, 10 -5 mol / L, 10 -4 mol / L and 10 -3 mol / L Adenosine relaxation of the basilar artery vascular 5-HT contraction percentage of 2.66 ± 6.90,8.21 ± 4.85,16.58 ± 10.47,37.99 ± 12.53,69.16 ± 11.74,78.99 ± 13.38. 10 -5 mol / L ,10-4mol / L and 10 -3 mol / L adenosine hypoxia and aerobic groups vasodilating effects significant difference (P lt; 0.05) suggesting that hypoxia can inhibit relaxation of vascular role of adenosine. 4 normoxic and hypoxic conditions adenosine receptor antagonist DPCPX on adenosine vasodilator effect SCH58261, MRS1191 are the adenosine A 1 , A 2 , A 3 receptor antagonists. The diastolic amplitude to the separate perfusion 10-4mol / L adenosine 5-HT vasoconstrictor 100% under normoxic conditions, 10 -6 mol / L DPCPX, 10 -6 mol / L SCH58261 and 10 -6 mol / L MRS1191 incubation, the relaxation percentage of 10-4mol of adenosine on the basilar arterial contraction in 5-HT were 98.35 ± 16.06,60.28 ± 14.08,96.66 ± 14.48. Under hypoxic conditions, 10 -6 mol / L DPCPX, 10 -6 mol / L SCH58261 and 10 -6 mol / L MRS1191 incubated After 10 -4 mol adenosine 5-HT contraction of the basilar artery vascular relaxation percentage were 75.39 ± 7.98,42.37 ± 11.25,72.38 ± 8.21. These results suggest that DPCPX and MRS1191 vasodilator role of adenosine in normoxic or hypoxic conditions no significant effect, while SCH58261 significantly inhibit adenosine vasodilatory effect (P lt; 0.05). Tip of adenosine by acting on adenosine A 2 receptor which play diastolic rat cerebrovascular role. 5 hypoxia on adenosine A 2 receptor antagonists inhibit the the adenosine vasodilator effect and separate perfusion -4 mol / L adenosine on the 5-HT contraction vascular relaxation by 100%, the normoxic state 10 -9 mol / L, 10 -8 mol / L, 10 -7 mol / L, 10 -6 mol / L SCH58261 incubated for 10 -4 mol adenosine 5-HT contraction of the basilar artery vascular relaxation percentage, respectively, 91.12 ± 8.53, 84.12 ± 9.15,71.88 ± 9.89,60.28 ± 14.08. Under anoxic conditions -9 mol / L, the 10 -8 mol / L, 10 -7 mol / L, 10 -6 mol / L SCH58261 After incubation the diastolic Percentage of the of 10-4mol adenosine of the basilar artery contraction of 5-HT, respectively, 68.72 ± 6.75,64.92 ± 10.53,56.62 ± 8.42,42.37 ± 11.25. Compared between the two groups a significant difference (P lt; 0.05), the experimental results show that hypoxia can significantly enhance the SCH58261 inhibition of the 10-4mol adenosine vasodilator effect, prompted hypoxia by inhibit adenosine A 2 receptor thereby inhibiting the relaxation of vascular effects of adenosine. Hypoxia in the adenosine A 2a receptor agonist diastolic cerebral vascular effects adenosine A 2 receptor CGS21680 affinity can be divided into A 2a , and A2b two subtypes. CGS21680 adenosine A 2a receptor selective agonist. Hypoxia can inhibit 10 -6 mol / L CGS21680 Shuzhang Ji bottom artery role. Normoxic state 10 -6 mol / L CGS21680 for 5-HT contraction of the maximum relaxation of the basilar arterial amplitude to 100%, under normoxic and hypoxic conditions 10 -6 < / sup> mol / L CGS21680 on 5-HT contraction of the basilar artery diastolic percentage was 99.77 ± 9.30,69.52 ± 12.97, respectively between the two groups there is a significant difference (P lt; 0.05). Prompted hypoxia by acting at adenosine A 2a receptor thereby inhibiting adenosine vasodilator effect. 7 wow Pakistan due to the vasodilatory role in hypoxia inhibition of adenosine under hypoxic conditions, incubation adenosine alone group, 10 -6 mol / L wow Pakistan due to the pre-incubation group, 10 - 3 mol / L wow Ba diastolic percentage due to the adenosine group pre-incubated for 5-HT contraction base arteries were 73.13 ± 12.41,57.73 ± 11.07,55.21 ± 10.93. 10 -6 mol / L and 10 -3 mol / L wow bar due can significantly inhibit adenosine under hypoxic conditions vasodilatory effect (P lt; 0.05) , suggesting that the Na / K pump may be involved in the inhibition of hypoxia relaxant effects of adenosine. Inhibition of high affinity sodium pump 10 -6 mol / L, and the inhibition of the master cylinder 10 -3 mol / L wow Pakistan due to inhibition of adenosine vasodilator effect significant difference in Step Na / K pump high affinity subunits involved in the inhibition of hypoxia on the adenosine vasodilatory effect. Under normoxic and hypoxic conditions, wow, Pakistan due 10 -6 mol / L group of adenosine vasodilator percentage was 72.64 ± 9.77,57.73 ± 11.07, both statistically significant (P lt; 0.05), showed that hypoxia can also significantly enhance the wow Pakistan due to inhibition of the the adenosine vasodilator effect of. These results suggest that hypoxia may by inhibiting Na / K pump activity thus inhibiting adenosine vasodilator role. Conclusion: 1 hypoxia adenosine able to concentration-dependent relaxation cerebrovascular contraction of the rat 5-HT, hypoxia can significantly inhibit the vasodilatory effects of adenosine, this inhibition by inhibiting adenosine on located on the vascular smooth muscle adenosine A 2a receptor role play. 2 in the hypoxic state, wow bar due to a significant inhibition of adenosine vasodilatory role, suggesting that of Na / K pump involved in the inhibition of hypoxia relaxant effects of adenosine, its high affinity subunits may be involved in hypoxia adenosine vasodilatory effects of inhibition. Hypoxia may by inhibiting Na / K pump activity thus inhibiting adenosine vasodilator effect.
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