Dakshinamurti K, Lal K J, Ganguly P K
Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Mol Cell Biochem. 1998 Nov;188(1-2):137-48.
The moderately pyridoxine (vitamin B6)-deficient male rat was introduced by us as an animal model (B6DHT) for the study of hypertension. Hypertension in this rat is associated with increased sympathetic stimulation. Arterial segments from B6DHT rats maintained a higher resting tone. The influx of 45calcium into intracellular compartment of the vascular smooth muscle of the caudate artery of B6DHT rats was also enhanced. Administration of pyridoxine attenuated the hypertension in B6DHT rats as well as in genetic or dietary-induced moderately hypertensive conditions such as in the Zucker obese rat and sucrose or low calcium-fed rats. However, pyridoxine did not have any effect on the spontaneously hypertensive rat. All classes of calcium channel blockers were effective in lowering the systolic blood pressure of B6DHT rats. The increased in vitro influx of 45calcium into intracellular compartment of artery segments of B6DHT rats as well as the BAY K 8644-induced influx of 45calcium into artery segments from normal rats were blocked by pyridoxal phosphate as well as by dihydropyridine-sensitive calcium channel blockers (DHP). Pyridoxal phosphate (PLP) in vitro enhances the binding of calcium channel antagonists to membrane preparations from vascular tissue. PLP corrects the membrane abnormality in responsive hypertensive conditions and thus, could be an endogenous modulator of DHP-sensitive calcium channels.
我们引入中度吡哆醇(维生素B6)缺乏的雄性大鼠作为研究高血压的动物模型(B6DHT)。该大鼠的高血压与交感神经刺激增加有关。B6DHT大鼠的动脉段维持较高的静息张力。B6DHT大鼠尾状动脉血管平滑肌细胞内45钙的流入也增强。给予吡哆醇可减轻B6DHT大鼠以及遗传性或饮食诱导的中度高血压状态(如Zucker肥胖大鼠和蔗糖喂养或低钙喂养大鼠)的高血压。然而,吡哆醇对自发性高血压大鼠没有任何作用。所有类型的钙通道阻滞剂均能有效降低B6DHT大鼠的收缩压。B6DHT大鼠动脉段细胞内45钙的体外流入增加以及BAY K 8644诱导的正常大鼠动脉段45钙流入均被磷酸吡哆醛以及二氢吡啶敏感钙通道阻滞剂(DHP)阻断。磷酸吡哆醛(PLP)在体外增强钙通道拮抗剂与血管组织膜制剂的结合。PLP纠正反应性高血压状态下的膜异常,因此可能是DHP敏感钙通道的内源性调节剂。