Ashmore R C, Rodman D M, Sato K, Webb S A, O'Brien R F, McMurtry I F, Stelzner T J
Division of Cardiology, University of Colorado, Health Sciences Center, Denver 80262.
Am J Physiol. 1991 Jun;260(6 Pt 2):H1929-34. doi: 10.1152/ajpheart.1991.260.6.H1929.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
我们最近描述了小鹿斑鼠（FHR）中肺动脉高压的早期出现，该动物患有血小板储存池疾病，且在后期会发展为系统性高血压。由于聚集的血小板释放的介质会影响血管张力，我们推测FHR中血小板介导的肺血管反应可能异常，并可能与肺动脉高压的机制有关。为了验证这一点，我们检查了来自患有中度严重肺动脉高压但体循环压力正常的年轻FHR的离体肺动脉（PA）和胸主动脉（Ao）的反应性。将这些血管与对照Sprague-Dawley大鼠（SDR）的PA和Ao进行比较。FHR的聚集血小板（1000 - 40000个血小板/mm³）导致SDR的PA和Ao扩张，但FHR的PA和Ao收缩。从SDR分离的血小板也观察到定性相似的反应，这意味着异常反应并非仅仅由于FHR中的储存池缺陷。FHR的PA对血小板衍生的内皮依赖性血管舒张剂ADP的反应明显受损，而FHR的Ao则轻度受损。FHR的PA对乙酰胆碱而非A23187的内皮依赖性舒张轻度受损，而FHR的Ao对两种舒张剂的反应均正常。FHR的PA和Ao对硝普钠的非内皮依赖性舒张均正常。FHR的PA对5-羟色胺的收缩敏感性增加，但对血栓素A2模拟物U-46619的收缩敏感性正常，而FHR的Ao对两种收缩剂的反应均正常。总之，患有自发性肺动脉高压的FHR的PA对正常和储存池缺陷血小板均表现出矛盾的收缩。（摘要截短于250字）
