Inhibition of left ventricular hypertrophy and normalization of cardiac contractile response in relation with oxidative stress in experimental hypertension

GOMEZ LLAMBI H; M DONATO; B BUCHHOLZ; G OTTAVIANO; G CAO; MULLER A; GELPI R; OTERO-LOSADA, MATILDE; MILEI J

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Congreso; 26th European Metting on Hypertension and Cardiovascular Protection; 2016

congresos y reuniones científicasTítulo:Inhibition of left ventricular hypertrophy and normalization of cardiac contractile response in relation with oxidative stress in experimental hypertensionAutor/es:GOMEZ-LLAMBI H.; DONATO M; BUCHHOLZ B; OTTAVIANO G; CAO G; MULLER A; GELPI R; OTERO-LOSADA M.; MILEI J.Lugar:RomeReunión:Congreso; European Society of Cardiology. Annual Congress; 2016Institución organizadora:European Society of CardiologyResumen:Introduction. Left ventricular hypertrophy (LVH) has been regarded to protect from heart failure, though this assumption is by now controversial. One of the key points is the role of the β-adrenergic pathway.Purpose.To evaluate whether: 1). chronic antihypertensive treatment may inhibit development of LVH and normalize impaired cardiac beta-adrenergic response, and 2).physiological improvement relates to changes in myocardial oxidative metabolism.Methods. Spontaneously hypertensive male rats (SHR, 2 months old) were assigned to different groups (n = 18/group) and treated (mg/kg, p.o) with: losartan 30 (L), hydralazine 11 (H), rosuvastatin 10 (R), carvedilol 20 (C) or water (control treatment). A control group for hypertension comprising 18 normotensive rats (Wistar-Kyoto, WKY) was also studied. Systolic blood pressure (SBP) (tail plethysmography in awake animals) and body weight (BW) were measured periodically. Euthanasia was administered at 16 months of treatment and 50% of the hearts were mounted in a Langendorff system. Left ventricular developed pressure (LVDP) and maximal rate of rise of left ventricular pressure (LV +dP/dtmax) were calculated as a measure of contractility in response to isoproterenol (Iso) 10-9 M, 10-7 M and 10-5 M. The other 50% of the hearts was conventionally processed for determination of immunolabeling of thioredoxins-1 (Trx-1), peroxyredoxin-2 (Prx-2) and glutaredoxin-3 (Grx-3) (antioxidant enzymes), caspase-3 (apoptosis indicator) and brain natriuretic peptide (BNP).Results. Body weight did not differ between groups. SBP (mmHg): 154±3 (L), 137±1 (H), 190±3 (R)**, 206±3 (SHR)*, 183±1 (C)**, 141±1 (WKY). High SBP was not correlated with LVH in group C. Contractile parameters were depressed at baseline in groups C, R, and SHR (1127±59, 1185±125 and 1035±94 respectively) compared with L, H and WKY (1591±126, 1408±111 and 1775±141) (penviar mensaje