| Kidney aminopeptidase A and hypertension, part I: spontaneously hypertensive rats. | |
MedLine Citation:
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PMID: 10024338 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Tissue and plasma levels of aminopeptidase A (APA), the principal enzyme that hydrolyzes angiotensin II (Ang II) to angiotensin III, were measured in spontaneously hypertensive rats (SHR) and their normotensive control strain at 3 different ages corresponding to prehypertensive (4 weeks), developing (8 weeks), and established (16 weeks) phases of hypertension. Plasma APA activity was significantly but modestly elevated in SHR at all 3 ages compared with normotensive Wistar-Kyoto rats. Likewise, levels of APA in brain, heart, and adrenal gland were generally, but again only moderately, elevated in SHR at all ages. However, a large increase in APA activity was seen within the kidney in which APA levels were elevated 41%, 51%, and 68% in SHR at 4, 8, and 16 weeks of age, respectively. Kidney APA levels were also significantly increased in immunoblots from 8- and 16-week-old SHR. Glomeruli isolated from 16-week-old SHR had 57% higher APA activity and increased immunoreactivity compared with Wistar-Kyoto rats. To determine whether the increase in kidney APA activity in SHR was related to Ang II levels, SHR were treated for 2 weeks with the angiotensin-converting enzyme inhibitor captopril. Captopril treatment reduced blood pressure to normotensive values and resulted in a 25% reduction in kidney APA activity. These results suggest that APA expression in the kidney may be regulated by activity of the renin-angiotensin system. If so, this would further suggest that upregulation of APA during conditions in which Ang II levels were elevated would have a protective effect against Ang II-mediated cardiovascular diseases, whereas a decrease in APA expression or a failure to upregulate would exacerbate such conditions. |
Authors:
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D P Healy; L Song |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Hypertension Volume: 33 ISSN: 0194-911X ISO Abbreviation: Hypertension Publication Date: 1999 Feb |
Date Detail:
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Created Date: 1999-03-09 Completed Date: 1999-03-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 7906255 Medline TA: Hypertension Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 740-5 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Mount Sinai School of Medicine of the City University of New York, NY, USA. d_healy@smtplink.mssm.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aminopeptidases
/
analysis,
metabolism* Animals Glutamyl Aminopeptidase Hypertension / enzymology*, physiopathology Kidney / enzymology*, physiopathology Male Rats Rats, Inbred SHR Rats, Inbred WKY Species Specificity Up-Regulation |
| Grant Support | |
ID/Acronym/Agency:
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HL42585/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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EC 3.4.11.-/Aminopeptidases; EC 3.4.11.7/Glutamyl Aminopeptidase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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