2001 Fiscal Year Final Research Report Summary
Involvement of prostanoid receptor in blood pressure and acute renal failure.
| Project/Area Number |
11671041
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Kidney internal medicine
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
ASANO Kenichiro Fukushima Medical University, Department of Medicine, Assistant Professor, 医学部, 助手 (20315659)
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| Co-Investigator(Kenkyū-buntansha) |
ASAHI Koichi Fukushima Medical University, Department of Medicine, Assistant Professor, 医学部, 助手 (60274966)
KATOH Tetsuo Fukushima Medical University, Department of Medicine, Lecturer, 医学部, 講師 (70194834)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Prostanoid / Receptor / Knockoutmouse / Acute renal failure / Hypertension |
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| Research Abstract |
The pathophysiological roles of the prostanoid receptors in the development of ischemic ARF or hypertension are not fully understood, partly because of the limited specificity of their inhibitors or antagonists. We investigated whether targeted disruption of the PGI_2 receptor (IP) or TXA_2 receptor (TP) genes confers susceptibility to renal ischemic-reperfusion injury or hypertensioin using IP and TP knockout mice. Serum creatinine concentration in TP knockout mice was not significantly different from that in wild-type controls. There were no significant histological differences between TP knockout and wild-type mice. Likewise, IP knockout mice showed no significant differences from the wild-type controls in creatinine concentration or hlstologicai damages. Baseline systolic blood pressure (SBP) was not different in TP(-/-) and in TP(+/+), while SBP in IP(-/-) was significantly lower than that of IP(+/+). With high salt diet, SBP in IP(-/-) mice gradually increased significantly. In contrast, SBP in IP(+/+), TP(-/-), or TP(+/+) mice remained unchanged throughout the period of salt loading. Urinary excretion of the stable metabolites of TXA_2 in TP(-/-) and IP(-/-) and PGI_2 in TP(-/-) were not different from those in their corresponding wild type mice on high salt diet for 3 weeks. However, urinary excretion of PGI_2 metabolites in IP(-/-) was significantly higher than that in the wild type mice on high salt diet, Lack of TP or IP had no influence on postischemic ARF in mice, Indicating that receptors for TXA_2 or PGI_2 may have minimal roles in the development of this mouse model of ischemic acute renal failure. These findings also support the notion that, IP may participate in the maintenance of baseline BP and that, upon salt loading, BP adaptation may take place, at least in part, via IP mediated signals. TP may play a minimal role in the SP regulation or salt sensitivity of BP.
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Research Products
(2 results)
