1989 Fiscal Year Final Research Report Summary
Vascular renin-angiotensin system in the genesis of hypertension.
| Project/Area Number |
63044140
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| Research Category |
Grant-in-Aid for Overseas Scientific Survey.
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | OSAKA MEDICAL COLLEGE |
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Principal Investigator |
MIYAZAKI Mizuo Prof.Dept. of Pharmacology, Osaka Medical College, 薬理学教室, 教授 (10047186)
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| Co-Investigator(Kenkyū-buntansha) |
DZAU Victor J. Prof. Division of Vascular Medicine & ATHerosclerosis Brigham & Women's Hospital, 内科学教室, 教授
ISHII Kenji Assistant Dept. of Pharmacology, Osaka Medical College, 薬理学教室, 助手 (50140132)
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| Project Period (FY) |
1988 – 1989
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| Keywords | Two-Kidney / One-clip Hypertension / Renin mRNA / Angiotensinogen mRNA / Vascular renin-angiotensin system / Gene expression |
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| Research Abstract |
The gene expression in renin-angiotensin system has been documented but its role in experimental chronic renovascular hypertension has not been elucidated. In this study, we examined tissue renin and angiotensinogen (ANG-N) mRNAs in 2-kidney, 1-clip (2K-1C) male Wistar rats 4 and 16 weeks after operation. Total RNA was extracted by the guanidine thiocyanate/CsCl method. The mRNAs of kidney renin and liver, brain and aortic ANG-N were quantified by Northern blot analysis using rat renin and ANG-N genomic DNA (supplied by Dr. K.R.Lynch), respectively.
After 2K-1C operation, the animals were hypertensive for 16 weeks. Plasma renin concentration was 3 fold higher 4 weeks after operation but not different after 16 weeks compared to the control value. Renin gene expression in the clipped kidney was significantly greater than that in the contralateral kidney in both 4 and 16 weeks hypertensive rats. ANG-N gene expression in the liver of 16 weeks-2KlC was 2.5 fold higher than that in control rats while those in brain and aorta were unchanged in this hypertensive model. Taken together, over-expression of the renin and ANG-N gene existed both in the early and chronic phases of 2K-1C hypertension in rats. As reported previously, vascular ACE activated in chronic phase contributed toward local over-production of ANG- II. Since, the present results revealed unchanged ANG-N expression in vascular wall, vascular supply of ANG I would not be increased. The vascular ACE might utilize ANG- I originated from circulating blood.
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