Ally Ahmmed, Nauli Surya M, Maher Timothy J
Department of Pharmaceutical Sciences, Lloyd L. Gregory School of Pharmacy, Palm Beach Atlantic University, 901 South Flagler Drive, West Palm Beach, FL 33416, USA.
Brain Res. 2005 Sep 7;1055(1-2):73-82. doi: 10.1016/j.brainres.2005.06.087.
The majority of human strokes involve an occlusion of the middle cerebral artery and subsequent damage to the brain tissues it perfuses. We have previously reported that reflex cardiovascular changes during a static muscle contraction are attenuated following transient middle cerebral artery occlusion (MCAO) and reperfusion [A. Ally, S.M. Nauli, T.J. Maher, Cardiovascular responses and neurotransmission in the ventrolateral medulla during skeletal muscle contraction following transient middle cerebral artery occlusion and reperfusion, Brain Res. 952 (2002) 176-187]. We hypothesized that the attenuation is a result of altered expression of neuronal nitric oxide synthase (nNOS) within the rostral (RVLM) and caudal ventrolateral medulla (CVLM). In this study, we have compared cardiovascular responses and nNOS protein expression within the four quadrants, i.e., left and right sides of both RVLM and CVLM in sham-operated rats (n = 10) and in rats with a temporary 90-min left-sided MCAO followed by 24 h reperfusion (n = 10). Increases in mean arterial pressure during a static muscle contraction were significantly attenuated in MCAO rats when compared to sham rats. The transient ischemia reduced nNOS expression within the ipsilateral RVLM quadrant compared to the contralateral RVLM or RVLM quadrants of control rats. In contrast, compared to sham rats and the right CVLM quadrant of MCAO rats, nNOS expression was significantly augmented in the ipsilateral CVLM in left-sided MCAO rats. These data suggest that the attenuation of cardiovascular responses during static muscle contraction in MCAO rats is partly due to a reduction in nNOS expression within the ipsilateral RVLM and an overexpression of nNOS abundance within the ipsilateral CVLM. Results demonstrate that nNOS expression within the medulla plays a significant role in mediating cardiovascular responses during static exercise in intact and pathophysiological conditions.
大多数人类中风涉及大脑中动脉闭塞以及随后其灌注的脑组织受损。我们之前曾报道，短暂性大脑中动脉闭塞（MCAO）和再灌注后，静态肌肉收缩期间的反射性心血管变化会减弱[A. Ally、S.M. Nauli、T.J. Maher，短暂性大脑中动脉闭塞和再灌注后骨骼肌收缩期间腹外侧延髓的心血管反应和神经传递，《脑研究》952（2002）176 - 187]。我们推测这种减弱是由于延髓头端（RVLM）和尾端腹外侧延髓（CVLM）内神经元型一氧化氮合酶（nNOS）表达改变所致。在本研究中，我们比较了假手术大鼠（n = 10）和左侧MCAO 90分钟后再灌注24小时的大鼠（n = 10）双侧RVLM和CVLM四个象限（即左侧和右侧）内的心血管反应和nNOS蛋白表达。与假手术大鼠相比，MCAO大鼠在静态肌肉收缩期间平均动脉压的升高明显减弱。与对侧RVLM或对照大鼠的RVLM象限相比，短暂性缺血使同侧RVLM象限内的nNOS表达降低。相反，与假手术大鼠和MCAO大鼠的右侧CVLM象限相比，左侧MCAO大鼠同侧CVLM内的nNOS表达显著增加。这些数据表明，MCAO大鼠在静态肌肉收缩期间心血管反应的减弱部分是由于同侧RVLM内nNOS表达减少以及同侧CVLM内nNOS丰度的过度表达。结果表明，延髓内的nNOS表达在完整和病理生理条件下的静态运动期间介导心血管反应中起重要作用。
