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The correlation of pharmacodynamic activity of mineralocorticoid receptor antagonism with its blood pressure lowering effect in rat with the remnant kidney
Author(s) -
Ma Xiuying,
Contino Lisa,
Stribling Sloan,
Chen Nancy,
Yi Pan,
Wang Li,
Price Olga,
Loewrigkeit Christopher,
Keohane Carol Ann,
Jochnowitz Nina,
Parlapiano Allison,
Gichuru Loise,
Ping Xiaoli,
Wickham Alexandra,
Szeto Daphne,
Crook Martin,
Pai Lee-Yuh,
Metzger Joseph
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.872.22
Subject(s) - natriuresis , kaliuresis , endocrinology , medicine , mineralocorticoid receptor , eplerenone , spironolactone , aldosterone , blood pressure , kidney
Blockade of aldosterone action on the kidney with mineralocorticoid receptor antagonist spironolactone (SPL) or eplerenone (EPL) leads to increased natriuresis and decreased kaliuresis and has proven clinically effective for the treatment of hypertension and heart failure. However, a direct correlation between blood pressure (BP) lowering and the increased natriuretic effect in response to chronic administration of MR antagonist has not been well characterized. In the present study, our goal was to understand whether MR antagonist induces increased natriuresis overtime and therefore correlates to BP lowering in a hypertensive rat model with renal mass reduction (remnant kidney). Animals with the remnant kidney developed sustained systemic hypertension (140–180 mmHg), and their BP and urine chemistry was continuously monitored before and during the drug treatment with vehicle or SPL (30–100mg/kg) administered orally for 4 weeks. Following the 4 week chronic administration of SPL, systolic BP was dose‐dependently reduced by up to 15 mmHg, which was also accompanied with a marked attenuation in proteinuria. However, SPL induced initial increases in natriuresis and decreases in kaliuresis were gradually diminished over the course of the study. These findings clearly demonstrate that the BP lowering effect of SPL is not correlated with its chronic natriuretic effect in the hypertensive rat with remnant kidney.