Mayhan W G, Faraci F M, Heistad D D
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, Iowa.
Hypertension. 1988 Dec;12(6):556-61. doi: 10.1161/01.hyp.12.6.556.
The goal of this study was to determine whether responses of cerebral arterioles to products released by platelets are impaired in stroke-prone spontaneously hypertensive rats (SHRSP). The diameter of pial arterioles was measured during suffusion with adenosine 5'-diphosphate (ADP), serotonin, and the thromboxane analogue U-46619, using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and SHRSP (7-10 months old). Responses of cerebral arterioles to ADP and serotonin were profoundly impaired in SHRSP. ADP (10(-5) M) increased pial arteriolar diameter 17 +/- 3% (mean +/- SE) in WKY and only 4 +/- 1% in SHRSP. Serotonin (10(-5) M) increased pial arteriolar diameter 15 +/- 2% in WKY and, in contrast, reduced the diameter 13 +/- 1% in SHRSP. Nitroglycerin produced a similar dilatation of cerebral arterioles in WKY and SHRSP, suggesting that impairment of dilatation in SHRSP in response to ADP and serotonin was not related to nonspecific impairment of vasodilatation in SHRSP. The thromboxane analogue U-46619 produced a similar constriction of arterioles in WKY and SHRSP. We also examined the possibility that impaired dilator responses of cerebral arterioles in SHRSP in response to ADP and serotonin may be related to production of a cyclooxygenase vasoconstrictor substance. Indomethacin (10 mg/kg i.v.) partially restored dilator responses to ADP and serotonin in SHRSP, without altering responses in WKY. Thus, we speculate that vasoactive substances released by platelets may release a prostanoid constrictor substance from cerebral vessels of SHRSP and thereby predispose SHRSP to cerebral ischemia and, perhaps, stroke.
本研究的目的是确定易患中风的自发性高血压大鼠（SHRSP）的脑小动脉对血小板释放产物的反应是否受损。在正常血压的Wistar-Kyoto大鼠（WKY）和SHRSP（7 - 10月龄）中，使用活体显微镜在灌注5'-二磷酸腺苷（ADP）、5-羟色胺和血栓素类似物U-46619期间测量软脑膜小动脉的直径。SHRSP中脑小动脉对ADP和5-羟色胺的反应严重受损。ADP（10⁻⁵ M）使WKY的软脑膜小动脉直径增加17±3%（平均值±标准误），而在SHRSP中仅增加4±1%。5-羟色胺（10⁻⁵ M）使WKY的软脑膜小动脉直径增加15±2%，相反，却使SHRSP的软脑膜小动脉直径减少13±1%。硝酸甘油在WKY和SHRSP中使脑小动脉产生类似的扩张，这表明SHRSP中对ADP和5-羟色胺反应的扩张受损与SHRSP中血管舒张的非特异性受损无关。血栓素类似物U-46619在WKY和SHRSP中使小动脉产生类似的收缩。我们还研究了SHRSP中脑小动脉对ADP和5-羟色胺的扩张反应受损可能与环氧化酶血管收缩物质产生有关的可能性。吲哚美辛（10 mg/kg静脉注射）部分恢复了SHRSP中对ADP和5-羟色胺的扩张反应，而未改变WKY中的反应。因此，我们推测血小板释放的血管活性物质可能从SHRSP的脑血管中释放出一种前列腺素收缩物质，从而使SHRSP易患脑缺血，甚至可能发生中风。
