TY  - JOUR
A1  - Koch, Vitali
A1  - Grünewald, Leon David
A1  - Gruber-Rouh, Tatjana
A1  - Martin, Simon
A1  - Eichler, Katrin
A1  - Booz, Christian
A1  - Yel, Ibrahim
A1  - Vogl, Thomas J.
A1  - Buchner, Kristina
A1  - Hagenmueller, Marco
A1  - März, Winfried
A1  - Frey, Norbert
A1  - Hardt, Stefan
A1  - Riffel, Johannes
T1  - Homoarginine treatment of rats improves cardiac function and remodeling in response to pressure overload
T2  - Fundamental & clinical pharmacology
N2  - Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Male Wistar rats (n = 136) underwent sham operation (SH) or aortic banding (AB). Both groups were equally divided into 14 subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME for 4 weeks. HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg−1·day−1. Combining 800 mg·kg−1·day−1 HA with spironolactone or lisinopril yielded additional effects, showing a positive correlation with LV ejection fraction (+33%, p = 0.0002) and fractional shortening (+41%, p = 0.0014). An inverse association was observed with collagen area fraction (−41%, p < 0.0001), myocyte cross-sectional area (−22%, p < 0.0001) and the molecular markers atrial natriuretic factor (−74%, p = 0.0091), brain natriuretic peptide (−42%, p = 0.0298), beta-myosin heavy chain (−46%, p = 0.0411), and collagen type V alpha 1 chain (−73%, p = 0.0257) compared to placebo-treated AB animals. Co-administration of HA and L-NAME was found to attenuate cardiac remodeling and prevent NO-deficient hypertension following AB. HA treatment has led to a dose-dependent improvement of myocardial function and marked histological and molecular changes in cardiac remodeling following AB. Combining HA with standard heart failure medication resulted in additional beneficial effects boosting its direct impact on heart failure pathophysiology.
KW  - amino acids
KW  - aortic stenosis
KW  - cardiac remodeling
KW  - heart failure
KW  - rats
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73527
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-735270
SN  - 1472-8206
VL  - 36
IS  - 6
SP  - 992
EP  - 1004
PB  - Wiley-Blackwell
CY  - Oxford [u.a.]
ER  -