Adkins W K, Barnard J W, Moore T M, Allison R C, Prasad V R, Taylor A E
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
J Appl Physiol (1985). 1993 Mar;74(3):982-8. doi: 10.1152/jappl.1993.74.3.982.
Previous studies indicate that adenosine attenuates phorbol myristate acetate-(PMA) induced canine lung injury, but the mechanism has not been explained. To evaluate adenosine's protective mechanism, isolated and blood-perfused dog lungs were challenged by PMA (50 micrograms) under control conditions and after both pre- and post-treatment with adenosine and pretreatment with 2-chloro-N6-cyclopentyladenosine (CCPA), 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680C), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; PD-116948), or isoproterenol. Injury was assessed by measurement of the capillary filtration coefficient (Kf,c), and pulmonary vascular resistance was measured. PMA increased the Kf,c (0.170 +/- 0.015 to 1.030 +/- 0.167 ml.min-1.cmH2O-1.100 g lung wet wt-1) and the total pulmonary vascular resistance (18.2 +/- 3.8 to 110.2 +/- 60.8 cmH2O.l-1.min.100 g lung wet wt). Pretreatment with adenosine, A2 agonist, A1 antagonist, and isoproterenol blocked the increase in Kf,c induced by PMA. These agents also slightly attenuated the resistance increase induced by PMA, with the exception of the A1 antagonist, which completely prevented the resistance increase (24.3 +/- 7.8 to 23.4 +/- 8.1 cmH2O.l-1.min.100 g lung wet wt). The A1 agonist also slightly attenuated the increase in Kf,c (0.174 +/- 0.022 to 0.486 +/- 0.128 ml.min-1.cmH2O-1.100 g lung wet wt-1) and did not affect the resistance increase. Posttreatment with adenosine did not significantly affect the changes induced by PMA. These data show that PMA-induced increases in capillary permeability in the isolated blood-perfused dog lung can be blocked by pretreatment with adenosine, which binds the adenosine A2 receptors.
先前的研究表明，腺苷可减轻佛波酯（PMA）诱导的犬肺损伤，但其机制尚未阐明。为评估腺苷的保护机制，在对照条件下以及用腺苷进行预处理和后处理、用2-氯-N6-环戊基腺苷（CCPA）、2-[对-(2-羧乙基)苯乙氨基]-5'-N-乙基羧酰胺基腺苷（CGS 21680C）、8-环戊基-1,3-二丙基黄嘌呤（DPCPX；PD-116948）或异丙肾上腺素进行预处理后，用PMA（50微克）对离体且经血液灌注的犬肺进行刺激。通过测量毛细血管滤过系数（Kf,c）评估损伤情况，并测量肺血管阻力。PMA使Kf,c升高（从0.170±0.015升高至1.030±0.167毫升·分钟-1·厘米水柱-1·100克肺湿重-1）以及总肺血管阻力升高（从18.2±3.8升高至110.2±60.8厘米水柱·升-1·分钟·100克肺湿重）。用腺苷、A2激动剂、A1拮抗剂和异丙肾上腺素进行预处理可阻断PMA诱导的Kf,c升高。这些药物也略微减轻了PMA诱导的阻力升高，但A1拮抗剂除外，它完全阻止了阻力升高（从24.3±7.8降至23.4±8.1厘米水柱·升-1·分钟·100克肺湿重）。A1激动剂也略微减轻了Kf,c的升高（从0.174±0.022升高至0.486±0.128毫升·分钟-1·厘米水柱-1·100克肺湿重-1），且不影响阻力升高。用腺苷进行后处理对PMA诱导的变化无显著影响。这些数据表明，在离体血液灌注的犬肺中，PMA诱导的毛细血管通透性增加可被与腺苷A2受体结合的腺苷预处理所阻断。
