Donoso M Verónica, López Rodrigo, Miranda Ramiro, Briones René, Huidobro-Toro J Pablo
Centro de Regulación Celular y Patología Prof. J. V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Unidad de Regulación Neurohumoral, Pontificia Universidad Católica de Chile, Santiago, Chile.
Am J Physiol Heart Circ Physiol. 2005 May;288(5):H2439-49. doi: 10.1152/ajpheart.00548.2004. Epub 2005 Jan 6.
Because adenosine is a vascular tone modulator, we examined the effect of adenosine and congeners in the vascular reactivity of isolated human placental vessels and in perfused cotyledons. We characterized its vasomotor action and tentatively identified the receptor subtypes and their intracellular signaling mechanisms. We recorded isometric tension from the circular layer of chorionic vessel rings maintained under 1.5 g of basal tension or precontracted with KCl. The relative order of potency of adenosine and structural analogs is consistent with the expression of A2B receptors, 5'-(N-ethylcarboxamido)adenosine (NECA) being the most potent. The maximal contraction ranged from 45% to 60% of the KCl standard response, except for an A2A receptor agonist that did not exceed 15%. Consistently, NECA was 100-fold more potent than adenosine to raise the perfusion pressure of ex vivo perfused cotyledons. In contrast, a selective A3 receptor agonist relaxed precontracted rings of chorionic vessels. Whereas a selective A3 receptor antagonist was ineffective to antagonize adenosine-induced contraction, A2 or A1 receptor antagonists reduced adenosine-induced vasoconstriction concentration-dependently. Denudation of the endothelial layer reduced adenosine- and NECA-induced contractions by 50-70%. Furthermore, indomethacin reduced adenosine- or NECA-induced contractions concentration-dependently in intact and endothelium-denuded rings. A thromboxane receptor antagonist blocked adenosine- and NECA-induced contractions in intact and endothelium-denuded rings, suggesting the involvement of an arachidonic acid metabolite as the mediator of the vasoconstriction. We propose that adenosine A2B receptors mediate the adenosine-induced contraction vasomotor effect in human chorionic vessels and that this involves synthesis of a thromboxane receptor activator or a related prostanoid.
由于腺苷是一种血管张力调节剂，我们研究了腺苷及其同系物对离体人胎盘血管和灌注的子叶血管反应性的影响。我们对其血管舒缩作用进行了表征，并初步确定了受体亚型及其细胞内信号传导机制。我们记录了在1.5 g基础张力下维持或用氯化钾预收缩的绒毛膜血管环环形层的等长张力。腺苷及其结构类似物的效价相对顺序与A2B受体的表达一致，5'-(N-乙基甲酰胺基)腺苷（NECA）最为有效。除了一种不超过15%的A2A受体激动剂外，最大收缩幅度为氯化钾标准反应的45%至60%。同样，NECA提高离体灌注子叶灌注压力的效力比腺苷高100倍。相比之下，一种选择性A3受体激动剂可使预收缩的绒毛膜血管环舒张。虽然一种选择性A3受体拮抗剂对拮抗腺苷诱导的收缩无效，但A2或A1受体拮抗剂可浓度依赖性地降低腺苷诱导的血管收缩。内皮剥脱使腺苷和NECA诱导的收缩减少50-70%。此外，吲哚美辛在完整和内皮剥脱的血管环中浓度依赖性地降低腺苷或NECA诱导的收缩。一种血栓素受体拮抗剂可阻断完整和内皮剥脱血管环中腺苷和NECA诱导的收缩，提示花生四烯酸代谢产物作为血管收缩的介质参与其中。我们提出，腺苷A2B受体介导腺苷在人绒毛膜血管中诱导的收缩血管舒缩作用，且这涉及血栓素受体激活剂或相关前列腺素的合成。
