| Budget Amount *help |
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1993: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
To study the role of calcium (Ca) sequestration by SR in small resistance artery to progression of hypertension in spontaneously hypertensive rats (SHR), we measured high-potassium-induced contraction in the superior mesenteric artery in SHR befor and after depleting sarcoplasmic reticulum (SR) Ca stores using ryanodine (Ry : SR Ca release channel opener) and thapsigargin (Tg : SR Ca-ATPase inhibitor). Isometric tension was measured in the rings of the first or second branch of the superior mesenteric artery in both 5-week-old (young) and 10-week-old (adult) SHR,and age matched Wistar-Kyoto rats (WKY).Responses induced by application of 40mM potassium for 5 minutes were measured before and after exposure to 10muM Ry or 1muM Tg. Systolic blood pressure was significantly higher in adult SHR than in the other groups. The magnitude of potassium-induced contraction was almost the same in both young strains, but significantly larger in SHR than in WKY in adult. After exposure to Ry or Tg, th
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e magnitude was slightly increased compared with the control contraction in young and adult WKY,but greatly increased in young and adult SHR.Moreover, the magnitude, after exposure to Ry or Tg, was significantly larger in adult SHR than in young SHR.The rate of relaxation after washout of potassium was almost the same in both young strains and adult strains, respectively. The rate after exposure to Ry or Tg was greatly delayd in SHR compared in WKY in both young and adult phases, and moreover, the time taken to reach over 50% of maximum relaxation after the agents was significantly delayd in adult SHR compared with young SHR.These results suggest that Ca sequestration by the SR in SHR was greater than in WKY,and both Ca influx from extracellular space and the Ca pump activity of SR in SHR increased age-dependently. Therefore, it is concluded that Ca pump in SR plays an important role in preventing the development and progression of hypertension in SHR via a buffering effect on the elevation of cytosolic free Ca. Less
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