Regional vascular responses to ATP and ATP analogues in the rabbit kidney in vivo:: roles for adenosine receptors and prostanoids
Regional vascular responses to ATP and ATP analogues in the rabbit kidney in vivo:: roles for adenosine receptors and prostanoids
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DOI：
10.1038/sj.bjp.0706901
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发表时间：
2006-11-01
影响因子：
7.3
通讯作者：
Evans, R. G.
中科院分区：
文献类型：
--
作者：
Eppel, G. A.;Ventura, S.;Evans, R. G.
背景和目的：我们对P2受体激活对肾血管张力影响的认识主要来自体外模型。我们的目的是研究ATP在体内肾循环中的药理学。实验方法：在戊巴比妥麻醉家兔，我们检查了总肾和髓质血管反应ATP（0.2和0.8 mg kg（-1）），β，γ-亚甲基ATP（β，γ- mATP，7和170 μ g kg（-1）），α，β-mATP（0.2和2 μ g kg（-1））和腺苷（2和6 μ g kg（-1））分别使用渡越时间超声和激光多普勒血流计。我们还确定了腺苷受体，NO或前列腺素类是否有助于嘌呤受体激动剂的行动。关键结果：肾动脉团的ATP，β，γ-mATP，和腺苷产生双相变化;缺血，然后充血，在总肾和髓质血流。α，β-mATP仅诱导缺血。腺苷受体拮抗剂8-（对磺苯基）茶碱降低腺苷的反应和仅ATP和β，γ- mATP的充血反应。NO合酶抑制（N-ω-硝基-L-精氨酸）没有显着改变对P2受体激动剂的反应。随后的环氧合酶抑制剂（布洛芬）减少了ATP和β，γ-mATP诱导的肾血流量增加。所有其他的反应保持不变。结论和影响：在兔肾在体内，α，β-mATP敏感受体介导血管收缩。β，γ-mATP和ATP至少部分通过腺苷受体诱导血管舒张。ATP诱导的肾血管舒张不依赖于NO，部分依赖于肾脏中的前列腺素类，但不依赖于控制髓质血流的血管系统。
Background and purpose: Our knowledge of the effects of P2-receptor activation on renal vascular tone comes mostly from in vitro models. We aimed to characterise the pharmacology of ATP in the renal circulation in vivo.Experimental approach: In pentobarbitone anaesthetized rabbits, we examined total renal and medullary vascular responses to ATP (0.2 and 0.8 mg kg(-1)), beta, gamma-methylene ATP (beta, gamma- mATP, 7 and 170 mu g kg(-1)), alpha, beta-mATP (0.2 and 2 mu g kg(-1)) and adenosine (2 and 6 mu g kg(-1)) using transit-time ultrasound and laser Doppler flowmetry, respectively. We also determined whether adenosine receptors, NO or prostanoids contribute to the actions of the purinoceptor agonists.Key results: Renal arterial boluses of ATP, beta, gamma-mATP, and adenosine produced biphasic changes; ischaemia followed by hyperaemia, in total renal and medullary blood flow. alpha, beta-mATP induced only ischaemia. The adenosine receptor antagonist 8-(p-sulphophenyl) theophylline reduced the responses to adenosine and the hyperaemic responses to ATP and beta, gamma- mATP only. NO synthase inhibition (N-omega-nitro-L-arginine) did not significantly alter responses to the P2 receptor agonists. Subsequent cyclooxygenase inhibition (ibuprofen) reduced the ATP- and beta, gamma- mATP-induced increases in renal blood flow. All other responses remained unchanged.Conclusions and implications: In the rabbit kidney in vivo, alpha, beta-mATP sensitive receptors mediate vasoconstriction. beta, gamma-mATP and ATP induce vasodilation at least partly through adenosine receptors. ATP induced renal vasodilatation is independent of NO and partly dependent on prostanoids in the bulk of the kidney, but not in the vasculature controlling medullary blood flow.