The role of plasmalemmal Ca^<2+> channels and intracellular Ca^<2+> stores in vascular smooth muscles during the development of vascular resistance

本研究探讨了质膜Ca^2+通道和肌浆网（SR）在血管平滑肌，特别是阻力血管张力形成中的作用。本研究的主要结果如下：1）Ca^<2+>通道和SR对胞浆Ca^<2+>（[Ca^<2+]i）的调节。本研究分析了SR功能调节剂ryanodine和cyclopiazonic acid对Fura-2测定的[Ca^<2+]i和大鼠肠系膜阻力动脉张力的影响。结果表明，在静息状态下，SR可作为一种缓冲剂降低[Ca^<2+>]i，而当跨膜Ca^<2 +>内流增加时，SR可通过释放Ca^<2 +>来放大收缩。当低浓度激动剂激活阻力血管α 1肾上腺素能受体时，电压依赖性Ca ^<2 +>通道（VDC）的Ca^<2 +>内流增强，但无任何去极化。高浓度的激动剂引起去极化，从而增强了钙离子通过VDC的内流，除此之外，还出现了钙离子通过VDC以外的途径内流。这种进入对K^+通道阻断剂敏感，但对二氢吡啶类Ca^<2+>通道阻断剂不敏感。3）高血压血管中离子通道的功能。在自发性高血压大鼠的血管平滑肌中，电压依赖性Ca^2+通道在静息状态下是活跃的，这产生了主动张力并激活了Ca^2+激活的K^+通道。增加Ca^2+内流可使SR中的Ca^2+增加，然后增加SR中的Ca^2+释放。

In this study, the roles of plasmalemmal Ca^<2+> channels and sarcoplasmic reticulum (SR), intracellular Ca^<2+> stores, in the development of tension in vascular smooth muscle, especially in resistance vessels, were investigated. The major findings are as follws.1) Regulation of cytoplasmic Ca^<2+> ([Ca^<2+>]i) by Ca^<2+> channel and SR.I analyzed the effects of ryanodine and cyclopiazonic acid, modifiers of SR functions, on [Ca^<2+>]i, mesured with fura-2, and the tension of rat mesenteric resistance arteries. The results suggest that SR plays as a buffer to decrease [Ca^<2+>]i at a resting state, while it amplifies a contraction by releasing Ca^<2+> when transmembrane Ca^<2+> influx increased.2) Ca^<2+> entry pathways following activation of alpha1-adrenoceptor. When alpha1-adrenoceptors of resistance vassels was activated by low concentration of agonist, Ca^<2+> influx through voltage-dependent Ca^<2+> channel (VDC) was enhanced without any depolarization. This influx triggered Ca^<2+> release from SR.A high concentration of agonist caused depolarization, which in turn enhanced the Ca^<2+> influx through VDC.Besides this, Ca^<2+> entry through a pathway other than VDC also occurred. This entry was sensitive to K^+ channel blockers but not to dihydropyridine Ca^<2+> channel blockers.3) Functions of ion channels in the hypertensive vessels. In vascular smooth muscles from spontaneously hypertensive rate voltage-dependent Ca^<2+> channels were active at the resting state, which produced an active tension and activated Ca^<2+>-activated K^+ channels. Increased Ca^<2+> influx provided more Ca^<2+> to SR, then increased Ca^<2+> release from SR.