Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
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Research Abstract |
We have examined the functional role of superficial sarcoplasmic reticulum (SR) of arterial smooth muscle in essential hypertension by comparing the effects of agents that interact with the SR function between spontaneously hypertensive rats (SHR) and normotensive Wister-Kyoto rats (WKY). In the resting state of femoral, large and small mesenteric and carotid arteries from SHR, these is a large Ca^<2+> influx via L-type Ca^<2+> channels, which resulted in a high cytosolic Ca^<2+> level. The large Ca^<2+> influx during rest in these arteries is strongly by Ca^<2+> uptake into the superficial SR by the SR Ca^<2+> -ATPase (superficial buffer barrier function). The Ca^<2+> taken up into the SR is continually extruded into the extracellular space : vectorial release via Ca^<2+> release channels of the SR towards the plasmalemma, followed by extrusion via the Ca^<2+>-ATPase and the Na+ - Ca^<2+> exchanger of the plasmalemma. During this process, Ca^<2+> -activated K^+ (K_<Ca>) channels are highly activated (Ca^<2+> sparks). Approximately 20 - 30 % if the maximum contraction is always opposed by this pathway. Other activation pathway(s) in the resting state of some arteries. In the arteries from WKY, the resting Ca^<2+> influx is also buffered by the SR, and the Ca^<2+> taken up into the SR is extruded into the extracellular space. During this process, however, the K_<Ca> channels are not activated. The total capacity of SR for Ca^<2+> storage is larger in the SHR arteries than in the WKY arteries. Thus, we conclude that in the resting state of SHR arteries, the greater part of Ca^<2+> that enters the cells from the extracellular space is first taken up into the superficial SR and is then released towards the plasmalemma, resulting in the activation of K_<Ca> channels. SHR arteries increase the total SR capacity in order to store Ca^<2+> and thereby offset the large Ca^<2+> influx during both rest and contraction.
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