Mayhan W G, Faraci F M, Baumbach G L, Heistad D D
Department of Physiology and Biophysics, University of Nebraska Medical Center, Omaha 68198.
Am J Physiol. 1990 Apr;258(4 Pt 2):H1138-43. doi: 10.1152/ajpheart.1990.258.4.H1138.
Our goal was to determine whether responses of cerebral arterioles are altered in aged rats. We examined responses of cerebral arterioles in adult (6-8 mo old) and aged (22-24) mo old) Wistar rats to superfusion of acetylcholine and bradykinin, which presumably produce dilatation by releasing an endothelium-derived relaxing factor (EDRF), and to nitroglycerin, which produces dilatation by a direct effect on vascular muscle. In adult rats, cerebral arterioles dilated by 11 +/- 2% (SE) to acetylcholine (10(-5) M) and by 21 +/- 3% to bradykinin (10(-7) M). In contrast, arterioles in aged rats dilated by only 3 +/- 1% to acetylcholine and by 7 +/- 3% to bradykinin. Vasodilatation in response to nitroglycerin was similar to adult and aged rats. We also examined responses of cerebral arterioles to products released by platelets (ADP, serotonin, and thromboxane). ADP (10(-4) M) increased pial arteriolar diameter by 26 +/- 5% in adults rats and only 12 +/- 3% in aged rats. Serotonin (10(-5) M) produced modest vasodilatation in adult rats (7 +/- 1%) but modest vasoconstriction in aged rats (-5 +/- 2%). Vasoconstriction in response to a thromboxane A2 analogue (U 46619) was similar in adult and aged rats. Indomethacin (10 mg/kg iv) did not affect responses to acetylcholine, serotonin, and ADP in aged rats. Thus dilator responses of cerebral arterioles to agonists that may release EDRF are altered in aged compared with adult rats. Impaired vasodilatation in aged rats does not appear to be related to production of a cyclooxygenase constrictor substance.
我们的目标是确定老年大鼠脑小动脉的反应是否发生改变。我们检测了成年（6 - 8月龄）和老年（22 - 24月龄）Wistar大鼠脑小动脉对乙酰胆碱和缓激肽超灌注的反应，乙酰胆碱和缓激肽可能通过释放内皮衍生舒张因子（EDRF）产生舒张作用，同时检测了对硝酸甘油的反应，硝酸甘油通过直接作用于血管平滑肌产生舒张作用。在成年大鼠中，脑小动脉对乙酰胆碱（10⁻⁵M）舒张11±2%（标准误），对缓激肽（10⁻⁷M）舒张21±3%。相比之下，老年大鼠的小动脉对乙酰胆碱仅舒张3±1%，对缓激肽舒张7±3%。对硝酸甘油的血管舒张反应在成年和老年大鼠中相似。我们还检测了脑小动脉对血小板释放产物（ADP、5-羟色胺和血栓素）的反应。ADP（10⁻⁴M）使成年大鼠软脑膜小动脉直径增加26±5%，而在老年大鼠中仅增加12±3%。5-羟色胺（10⁻⁵M）在成年大鼠中产生适度血管舒张（7±1%），但在老年大鼠中产生适度血管收缩（-5±2%）。对血栓素A2类似物（U 46619）的血管收缩反应在成年和老年大鼠中相似。吲哚美辛（10mg/kg静脉注射）不影响老年大鼠对乙酰胆碱、5-羟色胺和ADP的反应。因此，与成年大鼠相比，老年大鼠脑小动脉对可能释放EDRF的激动剂的舒张反应发生了改变。老年大鼠血管舒张功能受损似乎与环氧化酶收缩物质的产生无关。
