Document Detail

Effects of endothelin-A receptor antagonism on bilateral renal function in renovascular hypertensive rats.
MedLine Citation:
PMID:  11860525     Owner:  NLM     Status:  MEDLINE    
Recent studies indicated an enhanced expression of Endothelin (ET) in the kidney contralateral to the vascular clip in two-kidney, one-clip (2K-1C) Goldblatt hypertension. We proposed that the enhanced intrarenal ET production might be responsible for altered haemodynamic and excretory capability of the unclipped kidney (UK) of 2K-1C renovascular hypertensive rats. Therefore, we examined the changes in arterial pressure and split renal function in the clipped (CK) and UK simultaneously, in response to chronic administration of the selective ETA receptor blocker (A-127722), given orally at a dose of 30 mg/kg/day for 3 weeks starting from the beginning of the 4th week of clipping. Systolic pressure averaged 177 +/- 7 mmHg in control rats (n=15) and 164 +/- 9 mmHg in treated rats (n=16) and the difference was not statistically different. Glomerular filtration rate (GFR), renal plasma flow (RPF) and renal vascular resistance (RVR) in the UK were not different between control and treated groups. Data were then analyzed by classifying rats as moderate hypertensives (MAP < 180 mmHg), and severe hypertensives (MAP > 180 mmHg). In the moderately hypertensive group, average MAP was 143 +/- 5 mmHg and 138 +/- 4 mmHg in control (n=9) and treated (n=10) groups, respectively. In the severely hypertensive group, average MAP was 192 +/- 5 mmHg and 188 +/- 5 mmHg in control (n=6) and treated (n=6) groups, respectively. GFR and RPF were significantly improved in the UK of only the severely hypertensives who received the antagonist. However, the ET(A) antagonist blunted the sodium loss in both CK and UK of severely hypertensive rats. We conclude that ET(A) receptors do not play a role in the progression of hypertension in 2K-1C renovascular hypertensive rats. Yet, ET(A) receptors play an important role in altering renal hemodynamics of the unclipped kidneys in severe degrees of renovascular hypertension.
S Kassab; H Hamdy; T AbdulGhaffar; J P Granger
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Fundamental & clinical pharmacology     Volume:  15     ISSN:  0767-3981     ISO Abbreviation:  Fundam Clin Pharmacol     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2002-02-25     Completed Date:  2002-04-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  8710411     Medline TA:  Fundam Clin Pharmacol     Country:  France    
Other Details:
Languages:  eng     Pagination:  379-85     Citation Subset:  IM    
Department of Physiology, College of Medicine and Medical Sciences, Arabian Gulf University, Bahrain.
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MeSH Terms
Blood Pressure / drug effects
Diuresis / drug effects
Glomerular Filtration Rate / drug effects
Hemodynamics / drug effects
Hypertension, Renovascular / physiopathology*
Kidney / blood supply,  physiopathology*
Pyrrolidines / pharmacology
Rats, Sprague-Dawley
Receptor, Endothelin A
Receptors, Endothelin / antagonists & inhibitors*
Regional Blood Flow / drug effects
Sodium / urine
Vascular Resistance / drug effects
Grant Support
Reg. No./Substance:
0/A 127722; 0/Pyrrolidines; 0/Receptor, Endothelin A; 0/Receptors, Endothelin; 7440-23-5/Sodium

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