Document Detail

Acute renal failure in 2K2C Goldblatt hypertensive rats during antihypertensive therapy: comparison of an angiotensin AT1 receptor antagonist and clonidine analogues.
MedLine Citation:
PMID:  11350495     Owner:  NLM     Status:  MEDLINE    
1. This study compared the effect of a non-peptide angiotensin II receptor antagonist and a series of clonidine analogues on blood pressure and renal function in a two-kidney two-clip Goldblatt rat model of hypertension subjected to 2 weeks of dietary sodium deprivation. 2. Animals received either vehicle, the angiotensin II antagonist, ZD7155 or structural analogues derived from clonidine (AL-11, AL-12 and CN-10) at 10 mg kg-1 day-1 for 4 days. 3. All groups of rats had systolic blood pressure in the hypertensive range (160-180 mmHg). ZD7155 caused a 33-mmHg fall in blood pressure (P < 0.05) and raised plasma urea and creatinine four- to six-fold. 4. AL-12 decreased blood pressure by 30 mmHg (P < 0.05), but had no effect on water intake, urine flow or plasma urea and creatinine. AL-11 and CN-10 had minimal effects on blood pressure and water intake and while CN-10 decreased urine flow on the third treatment day, AL-11 markedly reduced urine flow by some 70%. 5. These data show that in this sodium deficient renovascular model of hypertension, blockade of angiotensin II receptors normalizes blood pressure but causes renal failure, whereas the vasodepressor action of the clonidine analogue AL-12 occurs without detriment to renal function. These findings imply that angiotensin II receptor antagonists could lead to renal failure if used as antihypertensive agents in renovascular hypertension whereas this would be avoided with the use of clonidine-like analogues.
M A Sattar; A P Yusof; E K Gan; T W Sam; E J Johns
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of autonomic pharmacology     Volume:  20     ISSN:  0144-1795     ISO Abbreviation:  J Auton Pharmacol     Publication Date:    2000 Oct-Dec
Date Detail:
Created Date:  2001-05-14     Completed Date:  2001-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8106455     Medline TA:  J Auton Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  297-304     Citation Subset:  IM    
School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
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MeSH Terms
Antihypertensive Agents / adverse effects*,  therapeutic use
Blood Pressure / drug effects
Clonidine / adverse effects,  analogs & derivatives*,  therapeutic use
Creatinine / blood
Diet, Sodium-Restricted
Hypertension, Renovascular / complications*,  drug therapy*,  physiopathology
Kidney Failure, Acute / etiology*,  physiopathology
Naphthyridines / adverse effects,  therapeutic use
Potassium / blood
Rats, Wistar
Receptor, Angiotensin, Type 1
Receptor, Angiotensin, Type 2
Receptors, Angiotensin / antagonists & inhibitors*
Sodium / blood
Urea / blood
Reg. No./Substance:
0/Antihypertensive Agents; 0/Naphthyridines; 0/Receptor, Angiotensin, Type 1; 0/Receptor, Angiotensin, Type 2; 0/Receptors, Angiotensin; 0/ZD 7155; 4205-90-7/Clonidine; 57-13-6/Urea; 60-27-5/Creatinine; 7440-09-7/Potassium; 7440-23-5/Sodium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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