Moderate exercise training provides left ventricular tolerance to acute pressure overload

Moreira-Goncalves D, Henriques-Coelho T, Fonseca H, Ferreira RM, Amado F, Leite-Moreira A, Duarte JA. Moderate exercise training provides left ventricular tolerance to acute pressure overload. Am J Physiol Heart Circ Physiol 300: H1044-H1052, 2011. First published December 24, 2010; doi: 10.1152/ajpheart.01008.2010.-The present study evaluated the impact of moderate exercise training on the cardiac tolerance to acute pressure overload. Male Wistar rats were randomly submitted to exercise training or sedentary lifestyle for 14 wk. At the end of this period, the animals were anaesthetized, mechanically ventilated, and submitted to hemodynamic evaluation with biventricular tip pressure manometers. Acute pressure overload was induced by banding the descending aorta to induce a 60% increase of peak systolic left ventricular pressure during 120 min. This resulted in the following experimental groups: 1) sedentary without banding (SED + Sham), 2) sedentary with banding (SED + Band), and 3) exercise trained with banding (EX + Band). In response to aortic banding, SED + Band animals could not sustain the 60% increase of peak systolic pressure for 120 min, even with additional narrowing of the banding. This was accompanied by a reduction of dP/dt(max) and dP/dt(min) and a prolongation of the time constant tau, indicating impaired systolic and diastolic function. This impairment was not observed in EX + Band (P < 0.05 vs. SED + Band). Additionally, compared with SED + Band, EX + Band presented less myocardial damage, exhibited attenuated protein expression of active caspase-3 and NF-kappa B (P < 0.016), and showed less protein carbonylation and nitration (P < 0.05). These findings support our hypothesis that exercise training has a protective role in the modulation of the early cardiac response to pressure overload

Ventricular BNP gene expression in acute cardiac overload

INTRODUCTION:B-type natriuretic peptide (BNP) plasma levels have important diagnostic and prognostic implications in heart failure (HF). Recently, aside from its natriuretic effect, antiproliferative and antifibrotic actions of BNP on the cardiovascular system have been described. Under physiological conditions the atria are the main source of this peptide, while its ventricular expression is still controversial. The aim of this work was to evaluate, in an animal model, the ventricular expression of BNP in normal hearts, at baseline and under acute cardiac overload.METHODS:Anesthetized open chest male Wistar rats (n=18) were instrumented with a micromanometer in the right ventricular cavity for pressure assessment. Randomization for three different protocols was then performed: (i) pressure overload for a period of 6 hours (SPr; n = 6), by pulmonary trunk banding, in order to double basal right ventricular systolic pressure; (ii) volume overload with a six-hour perfusion of Dextran 40 (SVol; n = 6), to raise end-diastolic right ventricular pressure fourfold; (iii) sham operated rats (n = 6). Transmural samples from the right ventricular free wall were then obtained for quantification of BNP mRNA by RT and quantitative real-time PCR. The results are expressed as mean+/-SEM (number molecules of mRNA BNP)/(ng total mRNA); p < 0.05.RESULTS:A basal expression of BNP was identified in the sham group (3.6x10(7) +/- 1.7x10(7)). BNP mRNA levels were elevated in both the SPr and SVol groups (+123.1 +/- 46.3% SPr and +171.6 +/- 87.7% SVol).CONCLUSIONS:Acute cardiac pressure and volume overload are associated with increased ventricular BNP gene expression. Our results suggest that BNP may be involved in early ventricular remodeling

Contractile effects of Ghrelin and expression of its receptor GHS-R1a in normal and hypertrophic myocardium

INTRODUCTION:Ghrelin, isolated in 1999, is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R1a). Recent studies suggest that it may influence the function of normal and failing hearts. Nonetheless, it has been difficult to differentiate its effects on the intrinsic properties of the myocardium from the secondary effects resulting from growth hormone release and vasomotor action. This study investigated the contractile effects of ghrelin and expression of its receptor GHS-R1a in normal and hypertrophic myocardium.METHODS:Adult Wistar rats randomly received monocrotaline (MCT; n=9; 60 mg/kg, s.c.) or vehicle (n=7; 1 ml/kg). Three weeks later, after right ventricular (RV) hemodynamic evaluation, the effects of 10(-6) M of a pentapeptide active fragment of ghrelin (fG) were tested on contractile parameters of RV papillary muscles (Normal, n=7; MCT, n=9). GHS-R1a mRNA expression was estimated in RV transmural free-wall samples (Normal, n=7; MCT, n=9), using real-time RT-PCR.RESULTS:In the Normal group, fG reduced active tension (AT), maximum velocity of tension rise (dT/dt(max)) and maximum velocity of tension decline (dT/dt(min)), by 27.9 +/- 4.0%, 28.5 +/- 6.7% and 21.4 +/- 4.2% respectively. In the MCT group, fG reduced AT, dT/dt(max) and dT/dt(min) by 24.1 +/- 6.3%, 24.3 +/- 6.5% and 24.5 +/- 6.1% respectively. GHS-R1a mRNA expression was similar in the two groups (Normal: 2.3*10(5) +/- 5.4*10(4); MCT: 3.0*10(5) +/- 1.1*10(5): p > 0.05).CONCLUSION:This study shows that ghrelin has negative inotropic and lusitropic effects. These effects and expression of its receptor are preserved in RV hypertrophy, suggesting that ghrelin may be a new target in progression to heart failure

Activation profile of pro-inflammatory cytokines in acute cardiac overload

INTRODUCTION:Pro-inflammatory cytokines have been implicated in ventricular remodeling during heart failure progression. In the present study, we investigated the effects of acute volume and RV pressure overload on biventricular hemodynamics and myocardial gene expression of IL-6 and TNF-alpha.METHODS:Male Wistar rats (n = 45) instrumented with RV and LV tip micromanometers were randomly assigned to one of three protocols: i) acute RV pressure overload (PrOv) induced by pulmonary trunk banding in order to double RV peak systolic pressure, for 120 or 360 min; ii) acute volume overload (VolOv) induced by dextran40 infusion (5 ml/h), for 120 or 360 min; iii) Sham. Free wall samples from the RV and LV were collected for mRNA quantification.RESULTS:In the RV, acute overload induced IL-6 and TNF-alpha gene expression, higher in VolOv (IL-6: + 669.7 +/- 263.4%; TNF-alpha: + 5149.9 +/- 1099.0%; 360 min) than in PrOv (IL-6: + 64.9 +/- 44.2%; TNF-alpha: + 628.1 +/- 229.3%; 360 min). In PrOv, TNF-alpha mRNA levels in the LV were increased, in the absence of ventricular overload. IL-6 and TNF-alpha mRNA levels did not correlate in the LV, while in the RV a positive correlation was found (r = 0.574; p < 0.001).CONCLUSIONS:Acute cardiac overload induces overexpression of pro-inflammatory cytokines. This gene activation is not uniform, being higher in volume overload and involving both load-dependent and load-independent mechanisms

Time course and mechanisms of left ventricular systolic and diastolic dysfunction in monocrotaline-induced pulmonary hypertension

Although pulmonary hypertension (PH) selectively overloads the right ventricle (RV), neuroendocrine activation and intrinsic myocardial dysfunction have been described in the left ventricle (LV). In order to establish the timing of LV dysfunction development in PH and to clarify underlying molecular changes, Wistar rats were studied 4 and 6 weeks after subcutaneous injection of monocrotaline (MCT) 60 mg/kg (MCT-4, n = 11; MCT-6, n = 11) or vehicle (Ctrl-4, n = 11; Ctrl-6, n = 11). Acute single beat stepwise increases of systolic pressure were performed from baseline to isovolumetric (LVPiso). This hemodynamic stress was used to detect early changes in LV performance. Neurohumoral activation was evaluated by measuring angiotensin-converting enzyme (ACE) and endothelin-1 (ET-1) LV mRNA levels. Cardiomyocyte apoptosis was evaluated by TUNEL assay. Extracellular matrix composition was evaluated by tenascin-C mRNA levels and interstitial collagen content. Myosin heavy chain (MHC) composition of the LV was studied by protein quantification. MCT treatment increased RV pressures and RV/LV weight ratio, without changing LV end-diastolic pressures or dimensions. Baseline LV dysfunction were present only in MCT-6 rats. Afterload elevations prolonged tau and upward-shifted end-diastolic pressure dimension relations in MCT-4 and even more in MCT-6. MHC-isoform switch, ACE upregulation and cardiomyocyte apoptosis were present in both MCT groups. Rats with severe PH develop LV dysfunction associated with ET-1 and tenascin-C overexpression. Diastolic dysfunction, however, could be elicited at earlier stages in response to hemodynamic stress, when only LV molecular changes, such as MHC isoform switch, ACE upregulation, and myocardial apoptosis were present.Supported by Portuguese grants from FCT (POCI/SAU-FCF/60803/2004 and POCI/SAU-MMO/61547/2004) through Cardiovascular R&D Unit (FCT No. 51/94)

Endogenous production of ghrelin and beneficial effects of its exogenous administration in monocrotaline-induced pulmonary hypertension

We investigated the endogenous production of ghrelin as well as cardiac and pulmonary vascular effects of its administration in a rat model of monocrotaline (MCT)-induced pulmonary hypertension (PH). Adult Wistar rats randomly received a subcutaneous injection of MCT (60 mg/kg) or an equal volume of vehicle. One week later, animals were randomly assigned to receive a subcutaneous injection of ghrelin (100 mug/kg bid for 2 wk) or saline. Four groups were analyzed: normal rats treated with ghrelin (n = 7), normal rats injected with saline (n = 7), MCT rats treated with ghrelin (n = 9), and MCT rats injected with saline (n = 9). At 22-25 days, right ( RV) and left ventricular (LV) pressures were measured, heart and lungs were weighted, and samples were collected for histological and molecular analysis. Endogenous production of ghrelin was almost abolished in normal rats treated with ghrelin. In MCT-treated animals, pulmonary expression of ghrelin was preserved, and RV myocardial expression was increased more than 20 times. In these animals, exogenous administration of ghrelin attenuated PH, RV hypertrophy, wall thickening of peripheral pulmonary arteries, and RV diastolic disturbances and ameliorated LV dysfunction, without affecting its endogenous production. In conclusion, decreased tissular expression of ghrelin in healthy animals but not in PH animals suggests a negative feedback in the former that is lost in the latter. A selective increase of ghrelin mRNA levels in the RV of animals with PH might indicate distinct regulation of its cardiac expression. Finally, ghrelin administration attenuated MCT-induced PH, pulmonary vascular remodeling, and RV hypertrophy, indicating that it may modulate PH

Monitoramento das pragas da videira no contexto da produção integrada de frutas.

Para a implementação do MIP no cultivo da uva, torna-se indispensável o monitoramento das pragas, realizado mediante amostragens periódicas, nos diferentes estágios fenológicos da cultura

Acute changes of biventricular gene expression in volume and right ventricular pressure overload

Objective: We investigated the effects of acute volume and RV pressure overload on biventricular function and gene expression of BNP, proinflammatory cytokines (IL-6 and TNF-alpha), iNOS, growth factors (IGF-1, ppET-1), ACE and Ca2+-handling proteins (SERCA2a, phospholamban and calsequestrin). Methods: Male Wistar rats (n =45) instrumented with pressure tip micromanorneters in right (RV) and left ventricular (LV) cavities were assigned to one of three protocols: i) Acute RV pressure overload induced by pulmonary trunk banding in order to double RV peak systolic pressure, during 120 or 360 min; ii) acute volume overload induced by dextran40 infusion (5 ml/h), during 120 or 360 min; iii) Sham. RV and LV samples were collected for mRNA quantification. Results: BNP upregulation was restricted to the overloaded ventricles. TNF-alpha, IL-6, ppET-1, SERCA2a and phospholamban gene activation was higher in volume than in pressure overload. IGF-1 overexpression was similar in both types of overload, but was limited to the RV. TNF-alpha and CSQ mRNA levels were increased in the non-overloaded LV after pulmonary trunk banding. No significant changes were detected in ACE or iNOS expression. RV end-diastolic pressures positively correlated with local expression of BNP, TNF-alpha, IL-6, IGF- 1, ppET-1 and SERCA2a, while RV peak systolic pressures correlated only with local expression of IL-6, IGF-1 and ppET-1. Conclusions: Acute cardiac overload alters myocardial gene expression profile, distinctly in volume and pressure overload. These changes correlate more closely with diastolic than with systolic load. Nonetheless, gene activation is also present in the non-overloaded LV of selectively RV overloaded hearts