Stewart L, Hamilton C, Ingwall J, Naomi S, Graves S, Canessa M, Williams G, Hollenberg N
Department of Medicine, Harvard Medical School, Boston, Mass.
Circ Res. 1993 Dec;73(6):1113-20. doi: 10.1161/01.res.73.6.1113.
Smooth muscle responses to Na+ pump inhibition are thought to reflect two elements: a neurogenic contribution, involving catecholamine release from nerve terminals, and a myogenic response, attributed to relations between pump activity, [Na+]i, and [Ca2+]i. In the present study, we describe the time course and magnitude of cell Na+ changes, assessed by two methods, atomic absorption and nuclear magnetic resonance spectroscopy during the myogenic contractile response of rabbit aorta strips to ouabain. A threshold concentration of 3 x 10(-7) mol/L induced a gradual rise in [Na+]i. Both methods showed an essentially identical monotonic rise over 4 to 8 hours from a baseline level of 8 to 10 mmol/L water to a peak, which was approximately fivefold higher. The neurogenic (rapid) and myogenic (delayed and gradual) contractile responses were temporally distinct. Ouabain at 10(-7) mol/L, a concentration 10- to 100-fold lower than the threshold for catecholamine-dependent rapid-onset responses, induced only a delayed and gradual contractile response, which reached a maximum at 6 to 8 hours. With 10(-6) mol/L ouabain, the delayed response of 1.6 +/- 0.2 g peaked at 7.3 +/- 1.1 hours and was sustained for 16 hours. The time course was similar to that for change in [Na+] but somewhat later. Ouabain at 10(-5) and 10(-4) mol/L induced a delayed response that was identical in magnitude but also induced an early rapid contractile response, which was prevented by reserpine or phentolamine pretreatment. These agents did not influence the delayed response.(ABSTRACT TRUNCATED AT 250 WORDS)
一种神经源性作用,涉及从神经末梢释放儿茶酚胺,以及一种肌源性反应,归因于泵活性、细胞内钠离子浓度([Na+]i)和细胞内钙离子浓度([Ca2+]i)之间的关系。在本研究中,我们描述了通过原子吸收和核磁共振波谱两种方法评估的细胞内钠离子变化的时间进程和幅度,该变化发生在兔主动脉条对哇巴因的肌源性收缩反应过程中。3×10⁻⁷mol/L的阈值浓度诱导[Na+]i逐渐升高。两种方法均显示,从8至10mmol/L水的基线水平开始,在4至8小时内[Na+]i呈基本相同的单调升高,直至达到约为基线五倍的峰值。神经源性(快速)和肌源性(延迟且逐渐)收缩反应在时间上是不同的。10⁻⁷mol/L的哇巴因,其浓度比依赖儿茶酚胺的快速发作反应阈值低10至100倍,仅诱导延迟且逐渐的收缩反应,该反应在6至8小时达到最大值。使用10⁻⁶mol/L哇巴因时,1.6±0.2g的延迟反应在7.3±1.1小时达到峰值,并持续16小时。时间进程与[Na+]变化相似,但稍晚一些。10⁻⁵和10⁻⁴mol/L的哇巴因诱导出幅度相同的延迟反应,但也诱导出早期快速收缩反应,利血平或酚妥拉明预处理可阻止该反应。这些药物不影响延迟反应。(摘要截短于250字)