Basal and ß-adrenergic cardiomyocytes contractility dysfunction induced by dietary protein restriction is associated with downregulation of SERCA2a expression and disturbance of endoplasmic reticulum Ca2+ regulation in rats.

BACKGROUND: The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR) are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and ß-adrenergic contractility in murine ventricular cardiomyocytes. METHODS: After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20) and a protein-restricted group (PRG, n = 20), receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV) were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca(2+)sparks analysis. RESULTS: PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after ß-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca(2+)sparks were observed in PRG cardiomyocytes. CONCLUSION: The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the ß-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca(2+) intracellular kinetics.

Cardiovascular and electrocardiographic parameters after tonin administration in Wistar rats.

In order to understand the mechanisms of interaction between tonin-angiotensin and renin-angiotensin systems (RAS) we evaluated, "in vivo" and "in vitro", in Wistar rats, cardiovascular and electrocardiographic parameters after tonin administration. Arterial pressure (AP) and electrocardiogram (ECG) were recorded in awake animals before and after tonin administration. Langendorff technique was used to analyze cardiac function in isolated heart in the presence of tonin and video motion edge detection system was used to evaluate the effect of tonin upon contractile function of isolated rat ventricular cardiomyocytes. After tonin infusion rats presented significantly higher diastolic and mean arterial pressure (MAP) and heart rate (HR) as compared with control. The ECG analysis revealed shorter RR interval, increase in the low-frequency (LF) range of the heart rate variability (HRV) power (%) and decrease in the high-frequency (HF) of HRV power (%). Isolated hearts perfused with tonin presented an increase in the arterial coronary pressure (ACP) and decline in the ventricular systolic tension (ST), maximal (dT/dt+) and minimal (dT/dt) contractility. The rates of contraction and relaxation of isolated ventricular cardiomyocytes were significantly increased due to the presence of tonin. The angiotensin II (Ang II) levels in the coronary sinus effluent increased in the presence of tonin in a dose-dependent manner and the effect of tonin upon ACP was completely blocked by candesartan. Tonin is able to generate the vasoconstrictor peptide Ang II in the isolated heart of the rat and the cardiovascular response induced by tonin was completely blocked by candesartan, an indication that the action of Ang II on Ang II type 1 (AT1) receptors is the major mechanism of the heart effects. Tonin affects cardiomyocyte contractile function which may be due to interference with Ca(2+) handling.

Chronic exercise partially restores the transmural heterogeneity of action potential duration in left ventricular myocytes of spontaneous hypertensive rats.

Hypertension leads to electrophysiological changes in the heart. Chronic exercise induced by a treadmill-running programme (TRP) is considered a potential non-pharmacological treatment for hypertension and may have implications in heart remodelling. However, it is not known whether the TRP is able to improve the electrophysiological properties of the heart in spontaneously hypertensive rats (SHR). In the present study, we investigated whether TRP affects the electrical properties of left ventricular (LV) myocytes isolated from different layers of the LV wall of SHR. Male SHR were divided into exercised (chronic treadmill running for 8 weeks; CEX-SHR) and sedentary (SED-SHR) groups. Age-matched normotensive Wistar male rats served as controls. Action potentials (AP) and transient outward potassium current (I(to) ) were recorded in subepicardial (EPI) and subendocardial (ENDO) LV myocytes. In normotensive controls, AP duration (APD) was longer in ENDO cells than in EPI cells. This sort of transmural heterogeneity in the LV was not observed in sedentary SHR and was partially restored in SHR subject to chronic exercise. This partial recovery was associated with an increase in I(to) density in EPI cells but not in ENDO cells. The electrophysiological changes observed in the CEX-SHR group were not accompanied by either amelioration of systolic blood pressure or a reduction in heart hypertrophy. These findings imply that a TRP is able to improve the electrophysiological parameters of isolated cardiac myocytes in SHR. This sort of adaptation contributes to the overall improvement of heart physiology in this model.

Exercise capacity is related to calcium transients in ventricular cardiomyocytes.

The aim of the present study was to evaluate the Ca2+ handling and contractility properties of cardiomyocytes isolated from rats with high intrinsic aerobic exercise capacity. Standard-performance (SP) and high-performance (HP) rats were categorized with a treadmill progressive exercise test according to the exercise time to fatigue (TTF). The SP group included rats with TTF between 16.63 and 46.57 min, and the HP group included rats with TTF>46.57 min. Isolated ventricular cardiomyocytes were dissociated from the hearts of SP and HP rats, and intracellular global Ca2+ ([Ca2+]i) transients were measured. The [Ca2+]i transient peak was increased in the HP group relative to the SP group (5.54+/-0.31 vs. 4.18+/-0.12 F/F0; P