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Mineralocorticoid receptor antagonism exhibits comparable BP lowering efficacy in Dahl salt sensitive rats with high vs. low renin and aldosterone tone
Author(s) -
Ma Xiuying,
Contino Lisa,
Price Olga,
Shuster Daniel,
Xu Ling,
Xue Jiyan,
Metzger Joseph
Publication year - 2013
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.27.1_supplement.1165.15
Subject(s) - spironolactone , endocrinology , medicine , aldosterone , plasma renin activity , mineralocorticoid receptor , excretion , chemistry , mineralocorticoid , antagonist , renin–angiotensin system , blood pressure , receptor
Spironolactone (SPL), a mineralocorticoid receptor (MR) antagonist is used for the treatment of hypertension and heart failure, acting through competitive binding of aldosterone (aldo), which has been shown to induce sustained increases in plasma renin activity (PRA) and aldo concentration (PAC) in the treated patients. In the present study, our goal was to evaluate SPL effect on blood pressure (BP) and renal function in hypertensive rat models with high vs. low PRA/PAC. Plasma/urine chemistry and BP was monitored in Dahl salt sensitive rats fed with low vs. high salt diet (LSD vs. HSD) before and after administration of SPL (100mg/kg/day) or placebo premixed in feed for 4 weeks. Compared to LSD, HSD for 3 weeks reduced PRA and suppressed PAC to unmeasurable levels. Following the 4 week chronic administration of SPL, animals fed LSD showed acute increase in Na+ excretion (2 fold), decrease in K+ excretion (Δ0.05mmol/mg), and sustained elevation of PAC/urinary aldo (3 fold) with no significant effect on PRA; animals fed HSD only exhibited acute decrease in K+ excretion (Δ0.04mmol/mg) with no effect on Na+ excretion and PRA/PAC. Interestingly animals fed LSD vs. HSD exhibited equivalent BP lowering (LSD, 155±4 vs. 143±3mmHg; HSD, 193±9 vs. 180±5mmHg, P<0.05 placebo vs. SPL). In conclusion, MR antagonism with SPL at the tested dose exhibits comparable BP lowering efficacy in hypertensive rats regardless of PRA/PRC levels.