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Effects of combination therapy with valsartan and aliskiren on arterial pressure, cardiac hypertrophy and urinary protein excretion in hypertensive rats
Author(s) -
Moniwa Norihito,
Varagic Jasmina,
Ahmad Sarfaraz,
Ferrario Carlos M.
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.1105.4
Subject(s) - aliskiren , valsartan , endocrinology , medicine , renin–angiotensin system , angiotensin ii , excretion , blood pressure , irbesartan , chemistry
We examined the effect of valsartan and aliskiren in 29 (12‐wk. old) male congenic mRen2. Lewis hypertensive rats following assignment to: vehicle (n=9), valsartan (30mg/kg/day; n=10) or valsartan combined with aliskiren (50mg/kg/day; n=10). Arterial pressure (AP) was measured by telemetry and concentrations of angiotensin‐(1–12) [Ang‐(1–12)], Ang II and Ang‐(1–7) in plasma, left ventricle (LV), kidney cortex and urine were measured by RIA 2 weeks after. Urinary angiotensinogen (U‐AGT) was measured by ELISA. Mean AP, LV weight and U‐protein excretion (UP) were reduced by valsartan and further reduced by the combined therapy. The increases in plasma Ang II induced with valsartan were reversed by the addition of aliskiren. Renal (R‐) Ang II was decreased and R‐Ang‐(1–7)/R‐Ang II ratio was increased in both treatment groups. UP correlated positively with R‐Ang II and negatively with R‐Ang‐(1–7)/R‐Ang II ratio while the reductions in U‐AGT and U‐Ang‐(1–12) in both treatment groups correlated with each other. We conclude that the more pronounced response induced by combined therapy is mediated in part through the blockade of renin and consequent decrease in Ang II levels. The changes of R‐Ang II or R‐Ang‐(1–7)/R‐Ang II ratio may explain the antiproteinuric effect of the combined therapy. This research was supported by PO1 HL 051952.