GTP_γS及GDP_βS对SHR_(sp)内脏阻力血管平滑肌钙通道的影响

Effects of GTP_γS and GDP_βS on Calcium Channels of Resistance Vascular Smooth Muscle Cells in SHRsp

目的研究G蛋白激动剂GTP_γS和抑制剂GDP_βS对卒中易惑型自发性高血压大鼠(SHR_(SP))及常压大鼠(Wistar)肠系膜动脉A_4～A_5分支阻力血管平滑肌钙通道的影响。方法应用膜片箝全细胞钡电流方式。结果 (1)GTP_γS使SHR_(SP)和Wistar两种大鼠阻力血管平滑肌全细胞峰值钡电流(peak IBa^(2+))明显增加,且SHR_(SP)大鼠显著大于wistar大鼠。GDP_βS则可抑制两种大鼠的全细胞峰值钡电流,对于SHR_(SP)大鼠的抑制程度显著大于对照Wistar大鼠。(2)GTP_γS使SHR_(SP)和Wis-tar两种大鼠阻力血管平滑肌钙通道稳态激活曲线右移,并且SHR_(SP)大鼠右移量显著大于wistar大鼠。GDP_βS也可使两种大鼠钙通道稳态失活曲线右移,SHR_(SP)的右移量在HP=-80mV时明显大于Wistar大鼠。结论 G蛋白可激活自发性高血压大鼠内脏阻力血管平滑肌电压依赖性钙通道。其作用特点有利于外钙内流,这可能是高血压时外周阻力增高的原因之一。

To investigate the effects of GTP_γS and GDP_βS on the whole-cell barium currents of voltage-dependent calcium channels (VDC) of the vascular smooth muscle cells (VSMC) from the A_4～A_5 branches in SHRsp mesenteric artery. Methods Using the wholecell Ba^(2+) current recording of the patch clamp technique. Results (1) GTP_γS, a G-protein agonist, increased whole-cell Ba^(2+) currents both of SHR_(sp) and Wistar, but SHR_(sp) with a higher ratio of amplitude change than Wistar. In addition, GTPrS shifted D_∞ to right both in SHR_(sp) and Wistar, but D_∞ shifted more in SHR_(sp) than that in Wistar. (2) GDP_βS, a G-protein antagonist, decreased whole-cell Ba^(2+) currents both of SHR_(sp) and Wistar, but SHR_(sp) with a higher inhibition ratio of amplitude change than Wistar. In addition, GDP_βS shifted F_∞ to right and in SHR_(sp) shifted more than control under HP=-80 m V. Conclusions The G-protein mechanism may promote Ca^(2+) influx and contribute to the increase of peripheral resistance during hypertension.