Abstract | BACKGROUND: Functional differences between the clipped and unclipped kidneys in a 2-kidney-1-clip (2K-1C) hypertension model have been reported. However, the molecular basis of these changes is poorly understood. OBJECTIVES: Expression of NHE-1 and NHE-3 isoforms and sodium pump activity (PNP), and their modulation by blood pressure (BP), PGE(2) and TXB(2) were examined in the kidneys of 2K-1C rats treated with cilazapril for short- (4 and 24 h) and long-term (7 days) periods. METHODS: 2K-1C rats were divided into two groups. Group 1 (short-term) animals were treated with a single dose of cilazapril for 4 or 24 h. Group 2 (long-term) animals received a daily dose of cilazapril for 7 days. 2K-1C animals receiving water served as clipped controls, and sham-operated animals were normal controls. Western blot analysis was used to estimate the protein levels and ELISA for PGE(2) and TXB(2). RESULTS: Levels of NHE-1 and NHE-3 protein in the unclipped kidneys of both treatment groups were increased, whereas levels of alpha-actin, PNP activity and crude microsomes remained unchanged. These changes were significantly reduced by long-term, and not by short-term treatment with cilazapril. In group 1 clipped kidneys, NHE-3 and alpha-actin proteins were increased, and crude microsomes and PNP activity were decreased. In group 2 clipped kidneys, both NHE-1 and 3 isoforms were induced, whereas PNP activity was decreased. Cilazapril did not reverse the changes in the clipped kidneys in both groups, but reduced the crude microsomes. Group 2 unclipped kidneys showed hypertrophy, which remained unaffected by cilazapril treatment. Induced levels of BP, PGE(2) and TXB(2) in both groups were reduced significantly except for the 24-hour post- cilazapril treatment. CONCLUSIONS: These findings demonstrate a differential expression of NHE-1 and NHE-3 isoforms which is dependent on the rise in BP, PGE(2) or TXB(2) in the long-term treatment group, but not in the short-term treatment group. Thus, the changes in NHE isoforms and sodium pump activity, together, contribute to functional differences that exist in the 2K-1C kidneys.
|
Authors | Islam Khan, Khaled K Al-Qattan, Majed A Alnaqeeb, Muslim Ali |
Journal | Nephron
(Nephron)
Vol. 92
Issue 2
Pg. 346-55
(Oct 2002)
ISSN: 1660-8151 [Print] Switzerland |
PMID | 12218313
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright 2002 S. Karger AG, Basel |
Chemical References |
- Angiotensin-Converting Enzyme Inhibitors
- Slc9a3 protein, rat
- Sodium-Hydrogen Exchanger 3
- Sodium-Hydrogen Exchangers
- growth factor-activatable Na-H exchanger NHE-1
- Cilazapril
- Thromboxane B2
- Sodium-Potassium-Exchanging ATPase
- Dinoprostone
|
Topics |
- Angiotensin-Converting Enzyme Inhibitors
(therapeutic use)
- Animals
- Blood Pressure
- Cilazapril
(therapeutic use)
- Dinoprostone
(blood)
- Hypertension, Renovascular
(drug therapy, metabolism, physiopathology)
- Kidney
(metabolism)
- Kidney Tubules, Proximal
(metabolism)
- Male
- Microsomes
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Sodium-Hydrogen Exchanger 3
- Sodium-Hydrogen Exchangers
(metabolism)
- Sodium-Potassium-Exchanging ATPase
(metabolism)
- Thromboxane B2
(blood)
|