Adenosine inhibits growth of rat aortic smooth muscle cells - Possible role of A(2b) receptor
Adenosine inhibits growth of rat aortic smooth muscle cells - Possible role of A(2b) receptor
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DOI：
10.1161/01.hyp.27.3.786
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发表时间：
1996-03-01
期刊：
影响因子：
8.3
通讯作者：
Jackson, EK
中科院分区：
文献类型：
--
作者：
Dubey, RK;Gillespie, DG;Jackson, EK
血管平滑肌细胞（SMC）的异常生长通常与高血压和动脉粥样硬化有关，正常血管内的稳态是通过血管收缩剂和血管舒张剂的平衡生成来维持的。此外，一些内源性血管收缩因子诱导 SMC 生长，而一些血管扩张剂则抑制 SMC 生长。由于腺苷是一种有效的血管扩张剂，因此它也可能抑制 SMC 生长。因此，腺苷（10（-8）至10（-3）mol/L）、2-氯腺苷（腺苷的稳定类似物；10（-8）至10（-3）mol/L）和8-溴-cAMP（10（-8）至10（-3）mol/L）对胎牛血清（FCS；2.5％）诱导的生长的影响对大鼠主动脉 SMC 进行了评估。通过测定DNA合成（用1μCi/mL [H-3]胸苷脉冲4小时的SMC中的胸苷掺入）和细胞增殖（细胞数量的变化）来分析生长。在存在和不存在腺苷、2-氯腺苷或8-溴-cAMP的情况下，用2.5% FCS处理生长停滞的SMC 24小时用于DNA合成或4天用于细胞增殖。所有三种物质均以浓度依赖性方式抑制 DNA 合成和细胞增殖。与腺苷相比，2-氯腺苷抑制生长的能力更强。 2-氯腺苷的抑制作用可被 KF17837（一种特异性 A(2) 受体拮抗剂）逆转，但不能被 DPCPX（一种特异性 A(1) 受体拮抗剂）逆转。此外，CGS21680（一种 A(2a) 受体激动剂）并未模仿 2-氯腺苷的抑制作用，并且 N-6-环戊基腺苷（CPA；一种 A(1) 受体激动剂）的作用并不明显比 2-氯腺苷更有效，表明腺苷的抑制作用可能是通过 A(2b) 受体介导的。这些研究提供了腺苷抑制 SMC 生长的证据，并表明局部腺苷水平的降低可能会启动 SMC 生长，并有助于在高血压和动脉粥样硬化中观察到的血管重塑过程。
Abnormal growth of vascular smooth muscle cells (SMC) is frequently associated with hypertension and atherosclerosis, and homeostasis within a normal vessel is maintained by the balanced generation of both vasoconstrictors and vasodilators. Moreover, several endogenous vasoconstricting factors induce SMC growth, whereas several vasodilators inhibit SMC growth. Inasmuch as adenosine is a potent vasodilator, it is possible that it too could inhibit SMC growth. Hence, the effects of adenosine (10(-8) to 10(-3) mol/L), 2-chloroadenosine (a stable analogue of adenosine; 10(-8) to 10(-3) mol/L), and 8-bromo-cAMP (10(-8) to 10(-3) mol/L) on fetal calf serum (FCS; 2.5%)-induced growth of rat aortic SMC were evaluated. Growth was analyzed by assaying DNA synthesis (thymidine incorporation in SMC pulsed for 4 hours with 1 mu Ci/mL [H-3]thymidine) and cell proliferation (change in cell number). Growth-arrested SMC were treated with 2.5% FCS in the presence and absence of adenosine, 2-chloroadenosine, or 8-bromo-cAMP for 24 hours for DNA synthesis or 4 days for cell proliferation. All three substances inhibited DNA synthesis and cell proliferation in a concentration-dependent manner. Compared with adenosine, 2-chloroadenosine was more potent in inhibiting growth. The inhibitory effects of 2-chloroadenosine were reversed by KF17837 (a specific A(2) receptor antagonist) but not by DPCPX (a specific A(1) receptor antagonist). Furthermore, the inhibitory effects of 2-chloroadenosine were not mimicked by CGS21680 (an A(2a) receptor agonist), and the effects of N-6-cyclopentyladenosine (CPA; an A(1) receptor agonist) were not markedly more potent than those of 2-chloroadenosine, suggesting that the inhibitory effects of adenosine are possibly mediated via A(2b) receptors. These studies provide evidence that adenosine inhibits SMC growth and suggest that a decrease in local levels of adenosine may initiate SMC growth and contribute to the vascular remodeling process observed in hypertension and atherosclerosis.