Shah J, Jandhyala B S
Department of Pharmacological & Pharmaceutical Sciences, University of Houston, TX 77204-5515, USA.
Clin Exp Hypertens. 1995 Jul;17(5):751-67. doi: 10.3109/10641969509033633.
We have previously demonstrated that cerebroventricular administrations (i.c.v) of potassium chloride solutions (KCl; 0.375-1.25 mumoles/5 microliters) elicit ouabain-sensitive, concentration-dependent decreases in the blood pressure and heart rates of anesthetized, normotensive Sprague-Dawley (SD) rats. These studies have suggested an inverse relationship between Na(+)-pump activity in the central nervous system (CNS) and central sympathetic outflow. Such a view is further supported by the present studies showing that i.c.v. injections of KCl failed to produce any alterations in the blood pressures of rats pretreated with an autonomic ganglionic blocker, chlorisondamine. In the present studies, depressor responses to i.c.v. potassium chloride were considered as functional indices for evaluation of neuronal Na(+)-pump activity in 8 and 12 week old (8 wk and 12 wk) SHR, WKY and Sprague-Dawley (SD) rats. Basal arterial blood pressures of 8 wk-old SD and SHR, and the responsiveness of these two groups to i.c.v. potassium chloride solutions are similar and they both are significantly greater than that of age matched WKY. However, in the 12 wk-old groups, arterial pressure of SHR was significantly greater than that of WKY as well as SD, whereas the depressor responses to KCl in SHR were significantly greater than that of only WKY. Pretreatment of the rats with i.c.v. ouabain abolished the differences in the hypotensive responses to i.c.v. potassium chloride that existed between various groups but not the differences in the basal blood pressures. Evaluation of these data suggest that a) the centrally mediated hypotensive responses to K+ in various groups could depend upon Na+, K(+)-pump activity in C.N.S. and/or on basal central sympathetic discharge; b) central sympathetic activity is greater in SHR only when compared to WKY but not to SD; c) since the central Na(+)-pump activity and sympathetic tone appears to be similar in SHR and SD, mechanisms other than the increases in sympathetic activity must play a prominent role in the development of spontaneous hypertension; d) attenuation of neuronal Na(+)-pump activity cannot account for greater sympathetic tone in SHR and SD-rats when compared to WKY.
我们之前已经证明，向脑室注射（脑室内注射）氯化钾溶液（KCl；0.375 - 1.25微摩尔/5微升）会引起麻醉的正常血压Sprague-Dawley（SD）大鼠的血压和心率出现哇巴因敏感的、浓度依赖性降低。这些研究表明中枢神经系统（CNS）中的钠泵活性与中枢交感神经输出之间存在负相关关系。本研究进一步支持了这一观点，即脑室内注射KCl未能使预先用自主神经节阻滞剂氯异吲哚铵处理的大鼠的血压产生任何变化。在本研究中，将对脑室内注射氯化钾的降压反应视为评估8周龄和12周龄（8 wk和12 wk）的自发性高血压大鼠（SHR）、Wistar-Kyoto大鼠（WKY）和Sprague-Dawley（SD）大鼠神经元钠泵活性的功能指标。8周龄的SD大鼠和SHR的基础动脉血压，以及这两组对脑室内氯化钾溶液的反应性相似，且二者均显著高于年龄匹配的WKY大鼠。然而，在12周龄组中，SHR的动脉血压显著高于WKY大鼠以及SD大鼠，而SHR对KCl的降压反应显著大于仅WKY大鼠。用脑室内注射哇巴因预处理大鼠消除了各组之间对脑室内氯化钾降压反应的差异，但未消除基础血压的差异。对这些数据的评估表明：a）各组对K + 的中枢介导的降压反应可能取决于中枢神经系统中的Na + 、K（+）-泵活性和/或基础中枢交感神经放电；b）仅与WKY大鼠相比时，SHR的中枢交感神经活性更高，但与SD大鼠相比则不然；c）由于SHR和SD大鼠的中枢钠泵活性和交感神经张力似乎相似，因此除交感神经活性增加之外的机制必然在自发性高血压的发展中起重要作用；d）与WKY大鼠相比，SHR和SD大鼠中神经元钠泵活性的减弱不能解释其更高的交感神经张力。
