| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2003: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
In pulmonary artery, combination treatment of BQ-123 and BQ-788 partially inhibited ET-1-induced contraction and increase in intracellular Ca^<2+> concentration ([Ca^<2+>]_i). However, pretreated with BQ-123 abolished ET-1-induced contraction and [Ca^<2+>]_i increase in renal artery. SNP, SNAP and forskolin reduced both ET-1-induced contraction and increase in [Ca^<2+>]_i in both pulmonary and renal arteries. However the effects were stronger in renal artery. ET-1-induced increase in [Ca^<2+>]_i was only partially attenuated by verapamil, whereas it reduced almost the half in renal arteries. ET-1-induced increase in [Ca^<2+>]_i in normal physiological salt solution (PSS) was reduced in Ca^<2+>-free PSS, and increase in [Ca^<2+>]_i of reapplication of CaCl_2 was not inhibited by nicardipine. Preincubation with Cyclopiazonic acid and thapsigargin inhibited ET-1-induced increase in [Ca^<2+>]_i in Ca^<2+>-free PSS, and also attenuated the ET-1-induced increase in [Ca^<2+>]_i. Phospholipase C (PLC) inhibitor U-73122 dramatically diminished both ET-1-induced increase in [Ca^<2+>]_i in Ca^<2+>-free PSS and subsequent application of CaCl_2. Treatment with 2APB and xestospongin C almost completely inhibit the induced increase in [Ca^<2+>]_i. Using RT-PCR, mRNA of TRPC1, TRPC4, TRPC5 TRPC6 and LTRPC7 were expressed in the tissue. These results demonstrate the presence of a receptor operated Ca^<2+>-influx controlled by downstream of PLC in the response of ET-1 in rat small pulmonary arteries.
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