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Significance Of Exaggerated Natriuresis After Angiotensin AT 1 Receptor Blockade Or Angiotensin‐ Converting Enzyme Inhibition In Obese Zucker Rats
Author(s) -
Tallam Lakshmi S,
Jandhyala Bhagavan S
Publication year - 2001
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2001.03457.x
Subject(s) - natriuresis , endocrinology , medicine , blockade , renin–angiotensin system , angiotensin converting enzyme , angiotensin ii , angiotensin receptor , receptor , chemistry , blood pressure
SUMMARY 1. Obese Zucker rats (OZR) were shown to be salt‐sensitive in that they develop hypertension when placed on a high‐salt diet. Because angiotensin (Ang) II is a major antinatriuretic factor, the present studies were undertaken to determine whether the characteristic of salt‐sensitivity of OZR is associated with an enhanced antinatriuretic function of endogenous AngII. 2. The extent of AngII‐mediated antinatriuresis was investigated in OZR and lean Zucker rats (LZR) using candesartan (100 μg/kg, i.v.), a selective angiotensin AT 1 receptor antagonist, and ramipril (1 mg/kg, i.v.), an angiotensin‐converting enzyme (ACE) inhibitor. The total number of AngII binding sites and their affinity were also assessed in renal cortical tubular membrane preparations of OZR and LZR using a specific radioligand‐binding assay. Plasma renin activity was determined using a standard radioimmunoassay. 3. Both candesartan and ramipril produced substantially greater increases in urinary sodium excretion and urine flow in OZR and these effects were significantly greater than those observed in LZR. These observations suggest that basal antinatriuretic function of endogenous AngII is exaggerated in OZR. 4. The functional overexpression of AngII was not due to any alterations in the affinity or the total number of AngII binding sites in renal cortical tubular membranes. Higher plasma renin values in the OZR could have contributed to the phenomenon. 5. In conclusion, marked diuresis and natriuresis after AT 1 receptor blockade and/or ACE inhibition suggest that the extent of endogenous AngII‐mediated sodium transport under basal conditions is greatly augmented in OZR. It is proposed this phenomenon may be a contributing factor for the salt‐ sensitivity in the OZR.