PARADOXICAL CONSTRICTION TO PLATELETS BY ARTERIES FROM RATS WITH PULMONARY-HYPERTENSION
PARADOXICAL CONSTRICTION TO PLATELETS BY ARTERIES FROM RATS WITH PULMONARY-HYPERTENSION
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DOI：
10.1152/ajpheart.1991.260.6.h1929
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发表时间：
1991-06-01
影响因子：
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通讯作者：
STELZNER, TJ
中科院分区：
文献类型：
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作者：
ASHMORE, RC;RODMAN, DM;STELZNER, TJ
我们最近描述了小鹿头大鼠（FHR）肺动脉高压的早期表现，这是一种患有血小板储存池病的动物，在晚年也会发生全身性高血压。由于血小板聚集释放的介质影响血管张力，我们假设FHR中血小板介导的肺血管反应可能是异常的，并可能与肺动脉高压的机制有关。为了验证这一点，我们检查了中重度肺动脉高压但体压正常的年轻FHR的分离肺动脉（PA）和胸主动脉（Ao）的反应性。这些血管与sd大鼠（SDR）的PA和Ao进行比较。FHR聚集血小板（1,000-40,000血小板/mm3）导致SDR PA和Ao扩张，而FHR PA和Ao收缩。从SDR中分离的血小板也观察到类似的定性反应，这意味着异常反应不仅仅是由于FHR储存池不足。对血小板来源的内皮依赖性血管扩张剂ADP的反应在FHR PA组明显受损，在FHR Ao组轻度受损。FHR PA对乙酰胆碱而非A23187的内皮依赖性扩张轻度受损，而FHR Ao对这两种扩张剂的反应正常。在FHR PA和Ao中，对硝普钠的内皮不依赖性扩张是正常的。在FHR PA中，收缩剂对5 -羟色胺的敏感性增加，但对血栓素A2模拟物U-46619的敏感性没有增加，而在FHR Ao中，两种收缩剂的敏感性均正常。综上所述，自发性肺动脉高压患者FHR的PAs对正常血小板和存储池缺陷血小板均表现出矛盾的收缩。这种矛盾的反应可能继发于ADP的血管舒张受损和收缩器对血清素的敏感性增强。在正常血压的FHR Ao中观察到类似的血小板聚集反应，这表明这些异常血管反应不能完全解释肺动脉高压继发血管损伤。
We recently described the early appearance of pulmonary hypertension in the fawn-hooded rat (FHR), an animal with platelet storage pool disease also known to develop systemic hypertension at later ages. Since mediators released from aggregating platelets influence vascular tone, we hypothesized that platelet-mediated pulmonary vascular responses in FHR may be abnormal and potentially linked to the mechanism of pulmonary hypertension. To test this we examined reactivity of isolated pulmonary arteries (PA) and thoracic aortas (Ao) from young FHR with moderately severe pulmonary hypertension but normal systemic pressures. These vessels were compared with PA and Ao from control Sprague-Dawley rat (SDR). Aggregating platelets (1,000-40,000 platelets/mm3) from FHR caused dilation of SDR PA and Ao but constriction of FHR PA and Ao. Qualitatively similar responses were also observed with platelets isolated from SDR implying that abnormal responses were not simply due to the storage pool deficiency in FHR. Response to the platelet-derived endothelium-dependent vasodilator ADP was markedly impaired in FHR PA and mildly impaired in FHR Ao. Endothelium-dependent dilation to acetylcholine, but not to A23187, was mildly impaired in FHR PA while responses to both dilators were normal in FHR Ao. Endothelium-independent dilation to sodium nitroprusside was normal in both FHR PA and Ao. Constrictor sensitivity to serotonin, but not to the thromboxane A2 mimetic U-46619, was increased in FHR PA while responses to both constrictors were normal in FHR Ao. In summary, PAs from FHR with spontaneous pulmonary hypertension exhibit paradoxical constriction to both normal and storage pool deficient platelets. This paradoxical response may be secondary to impaired vasodilation to ADP and enhanced constrictor sensitivity to serotonin. Qualitatively similar responses to aggregating platelets were observed in the normotensive FHR Ao, suggesting that these abnormal vascular responses are not fully explained by vascular injury secondary to pulmonary hypertension.