Phenylephrine induced hypertrophy in neonatal cardiac myocytes is modulated by testosterone

This study investigated the effect of nutrition on thedevelopment of left ventricular hypertrophy (LVH). C57BL/6J mice, aged 7 weeks, underwent either transverse aorticconstriction (TAC) or sham surgery (n=12/group). Then,animals were fed four different diets: control, high fat, highstarch, and high fructose. Left ventricular structure andfunction were assessed by echocardiography before and 5and 16 weeks after surgery. Banded animals fed the controlor high fat diet had the greatest heart weight to body weightratio (HW:BW), which was prevented by the high starchdiet.

HW:BW FS EF

ShamControl 5.41±0.15 0.27±0.02 63.05±2.04Fat 5.24±0.19 0.27±0.01 64.62±1.82Starch 5.53±0.14 0.29±0.02 66.01±2.66Fructose 5.21±0.18 0.32±0.03 68.73±2.94

BandedControl 6.97±0.63 0.24±0.03 55.09±4.08Fat 6.80±0.64 0.31±0.02 56.00±3.38Starch 5.19±0.33 0.51±0.05 78.52±2.55Fructose 5.82±0.38 0.29±0.03 63.89±3.10

Data are mean±SEM. Bold: P<0.05 compared to other banded groups andstarch sham. FS, fractional shortening; EF, ejection fraction.

Keywords: Hypertrophy; Nutrition; Echocardiography

doi:10.1016/j.yjmcc.2007.03.363

The effect of low dose tuna fish oil on cardiac hypertrophyand membrane fatty acid composition in the rat heartRenee Henry1, Peter L. McLennan2, Gregory E. Peoples1.1School of Health Sciences, Uni. of Wollongong, Australia.2Graduate School of Medicine, Uni. of Wollongong, Australia

Fish oil n-3 fatty acids have been implicated in the pre-vention of heart failure. This study evaluated the effect of lowdose fish oil (FO) on the development of cardiac hypertrophyand the effect of hypertrophy on membrane fatty acidincorporation. Hypertrophy development and myocardialfatty acid composition were determined 5w after aorticbanding or sham surgery in rats fed control diet (10% oliveoil, OO) or 0.3% FO (9.7% OO) diet for 9w. FO group 2 wasfed for 4w, starting 1w after surgery. Aortic banding surgeryresulted in a 20% increase in heart weight to tibia length ratioafter 5 weeks (mean±SEM sham vs. banded, 2.31±0.07 vs.2.78±0.07, p=0.001). Hypertrophy (+1.8%, p=0.797) wasnot significant in rats fed FO prior to banding but wassignificant in rats fed FO after surgery only (+15%, p=0.041).Hypertrophied hearts had higher membrane oleic acid (18:1n-9) content irrespective of dietary group but no other changes.FO diet markedly increased membrane DHA (22:6 n-3) (7.6±0.3 (OO n=15), 18.3±0.4 (FO n=15)), mainly in exchange

for arachidonic acid (20:4 n-6). The results show that therewas no preferential incorporation of DHA during newmembrane formation in hypertrophy, however the n-3 fattyacids prevented heart enlargement when incorporated prior tothe hypertrophic stimulus but not after. The results also showthat marked changes in myocardial membrane incorporationcan be produced by low dose FO (achievable in the humandiet, equivalent to 2 meals/w of salmon), which couldcontribute to reduced risk of heart failure seen with regularfish consumption.

Keywords: Cardiac hypertrophy; Fish oil; Membrane composition

doi:10.1016/j.yjmcc.2007.03.364

Phenylephrine induced hypertrophy in neonatal cardiacmyocytes is modulated by testosteroneRuchi Patel1, Rebecca H. Ritchie1,2, Igor R. Wendt1. 1MonashUniversity, Melbourne, Australia. 2Baker Heart ResearchInstitute, Melbourne, Australia

It is well recognized that sex-based differences exist in thedevelopment of cardiac hypertrophy. In this study, we hypo-thesized that both testosterone and dihydrotestosterone (DHT)would induce hypertrophic responses in male and femaleneonatal cardiac myocyte (NCM) cultures and exacerbate theresponse of these cells to phenylephrine (PE). Hypertrophy wasmeasured as an increase in protein synthesis. Testosterone10 nM and 1 μM had significantly differential effects on maleand female NCM (133±36 and 152±29% of control in maleNCM, n=6 and 69±17 and 77±11% of control in femaleNCM, n=6). In contrast, DHT 10 nM did not exert a hy-pertrophic response in either male or female NCM. Significant(p<0.05) hypertrophic responses were induced in both maleand female NCM treated with PE (20 μM, 153±17% of controlin male NCM, n=14 and 145±8% of control in female NCM,n=13). This PE response was significantly enhanced by pre-treatment of male and female NCM with 10 nM and 1 μMtestosterone (201±29 and 206±36% of control in male NCM,n=8 and 227±54 and 216±44% of control in female NCM,n=7), however, DHT had no effect on the PE response. Theseresults indicate that testosterone can modulate the hypertrophicresponse of cardiac myocytes. However, this may be via apathway independent of the androgen receptor as DHT had noeffect. These results also show that male and female neonatalcardiac myocytes can have differential responses to stimuli andthus the use of mixed sex neonatal cardiac myocyte culturesshould be carefully considered.

Keywords: Cardiac hypertrophy; Sex differences; Testosterone

doi:10.1016/j.yjmcc.2007.03.365

S138 ABSTRACTS / Journal of Molecular and Cellular Cardiology 42 (2007) S129–S144