Bari F, Errico R A, Louis T M, Busija D W
Department of Physiology and Pharmacology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, N.C. 27157-1083, USA.
J Vasc Res. 1997 Jul-Aug;34(4):312-20. doi: 10.1159/000159239.
We examined the effects of hypoxic/ischemic stress on cerebral arteriolar responses to oxytocin in anesthetized piglets. Pial arteriolar diameters were measured using a cranial window and intravital microscopy. First, we evaluated arteriolar responses to topical application of oxytocin during normoxic conditions. We then determined whether 5-10 min of arterial hypoxia, ischemia, or asphyxia alters oxytocin-induced responses. Arterial hypoxia was produced by inhalation of 7.5% O2-92.5% N2 for 10 min. Ischemia was achieved by increasing intracranial pressure for 10 min. Asphyxia was achieved by turning off the ventilator for 5 min. During normoxic conditions, oxytocin dilated pial arterioles by 9 +/- 1% at 10(-8) and by 16 +/- 1% at 10(-6) mol/l (n = 47, p < 0.05). Arteriolar responses to oxytocin did not change with repeated applications (n = 10). Following hypoxia, dilator effect of oxytocin was not changed at 10(-8) (8 +/- 2%) but it was reduced at 10(-6) mol/l (7 +/- 2%; p < 0.05, n = 8). After asphyxia or ischemia, oxytocin did not dilate arterioles at 10(-8) mol/l, whereas 10(-6) mol/l resulted in a mild vasoconstriction (-4 +/- 3 to -6 +/- 4%, n = 6 and 8). Topically applied superoxide dismutase did not preserve arteriolar responses to oxytocin after asphyxia although the arterioles did not constrict to 10(-6) mol/l oxytocin (n = 5). Dilatation of cerebral arterioles in response to oxytocin was reversed to constriction by N(omega)-nitro-L-arginine methyl ester (L-NAME) (15 mg/kg, i.v.; n = 5) and by endothelial impairment by intra-arterial infusion of phorbol ester (10[-5] mol/l; n = 5). We conclude that the absence of pial arteriolar dilation to oxytocin after ischemia and asphyxia indicates endothelial dysfunction which may be involved in the pathology of perinatal brain injury.
我们研究了缺氧/缺血应激对麻醉仔猪脑小动脉对催产素反应的影响。使用颅骨视窗和活体显微镜测量软脑膜小动脉直径。首先，我们评估了常氧条件下局部应用催产素时小动脉的反应。然后，我们确定5 - 10分钟的动脉缺氧、缺血或窒息是否会改变催产素诱导的反应。通过吸入7.5% O₂ - 92.5% N₂ 10分钟产生动脉缺氧。通过增加颅内压10分钟实现缺血。通过关闭呼吸机5分钟实现窒息。在常氧条件下，催产素在10⁻⁸ mol/l时使软脑膜小动脉扩张9±1%，在10⁻⁶ mol/l时扩张16±1%（n = 47，p < 0.05）。重复应用时，小动脉对催产素的反应不变（n = 10）。缺氧后，催产素在10⁻⁸ mol/l时的扩张作用不变（8±2%），但在10⁻⁶ mol/l时减弱（7±2%；p < 0.05，n = 8）。窒息或缺血后，催产素在10⁻⁸ mol/l时不使小动脉扩张，而10⁻⁶ mol/l导致轻度血管收缩（-4±3至-6±4%，n = 6和8）。局部应用超氧化物歧化酶在窒息后不能保留小动脉对催产素的反应，尽管小动脉对10⁻⁶ mol/l催产素不收缩（n = 5）。N(ω)-硝基-L-精氨酸甲酯（L-NAME，15 mg/kg，静脉注射；n = 5）以及动脉内输注佛波酯（10⁻⁵ mol/l；n = 5）导致的内皮损伤可使脑小动脉对催产素的扩张反应逆转为收缩。我们得出结论，缺血和窒息后软脑膜小动脉对催产素无扩张反应表明内皮功能障碍，这可能与围产期脑损伤的病理过程有关。
