Right Ventricle Of Rats Research Articles

Astaxanthin Supplementation Effects in Right Ventricle of Rats Exposed to Chronic Intermittent Hypobaric Hypoxia.

Thirty two male Wistar rats were randomly assigned to the following groups (n = 8 per group): the normoxia with vehicle (NX), normoxia with astaxanthin (NX + AS), chronic intermittent hypobaric hypoxia with vehicle (CIHH), and chronic intermittent hypobaric hypoxia with astaxanthin (CIHH + AS) groups. CIHH was simulated by 2 days in a hypobaric chamber followed by 2 days at sea level for 29 days. Exposure to CIHH induced RVH and increased lipid peroxidation (MDA), Nox2 expression, and SOD activity, however, it decreased pro-IL-1β expression. Astaxanthin restored oxidative stress markers (Nox2 and MDA), increased GPx activity, and decreased RVH compared to CIHH. Astaxanthin alleviates RVH and reduces Nox2 and MDA levels while increasing GPx activity in rats subjected to CIHH. These findings provide new insights of astaxanthin as a new nutraceutical against high-altitude effects.

Collagen Triple Helix Repeat-Containing Protein 1 Is a Novel Biomarker of Right Ventricular Involvement in Pulmonary Hypertension

BackgroundPulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension. MethodsA monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and patients with chronic thromboembolic pulmonary hypertension (CTEPH) (n = 64) before the first and after the final balloon pulmonary angioplasty. ResultsCTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was colocalized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human patients with pulmonary arterial hypertension (P = 0.006) and CTEPH (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = –0.213, P = 0.029), and right ventricular fractional area change (R = –0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH. ConclusionsCTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

Lower troponin expression in the right ventricle of rats explains interventricular differences in E-C coupling.

Despite distinctive functional and anatomic differences, a precise understanding of the cardiac interventricular differences in excitation-contraction (E-C) coupling mechanisms is still lacking. Here, we directly compared rat right and left cardiomyocytes (RVCM and LVCM). Whole-cell patch clamp, the IonOptix system, and fura-2 fluorimetry were used to measure electrical properties (action potential and ionic currents), single-cell contractility, and cytosolic Ca2+ ([Ca2+]i), respectively. Myofilament proteins were analyzed by immunoblotting. RVCM showed significantly shorter action potential duration (APD) and higher density of transient outward K+ current (Ito). However, the triggered [Ca2+]i change (Ca2+ transient) was not different, while the decay rate of the Ca2+ transient was slower in RVCM. Although the relaxation speed was also slower, the sarcomere shortening amplitude (ΔSL) was smaller in RVCM. SERCA activity was ∼60% lower in RVCM, which is partly responsible for the slower decay of the Ca2+ transient. Immunoblot analysis revealed lower expression of the cardiac troponin complex (cTn) in RVCM, implying a smaller Ca2+ buffering capacity (κS), which was proved by in situ analysis. The introduction of these new levels of cTn, Ito, and SERCA into a mathematical model of rat LVCM reproduced the similar Ca2+ transient, slower Ca2+ decay, shorter APD, and smaller ΔSL of RVCM. Taken together, these data show reduced expression of cTn proteins in the RVCM, which provides an explanation for the interventricular difference in the E-C coupling kinetics.

Abstract 13792: Integration of Proteomic and Transcriptomic Signatures in the Failing Right Ventricle of Rats With Monocrotaline Induced Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a chronic disease characterized by cellular remodeling in the pulmonary circulation. Pulmonary vascular obstruction, stiffening and constriction elevate pulmonary artery pressure and right ventricular (RV) afterload leading to failure (RVF). In a model of PAH induced by injection of monocrotaline (MCT, 60mg/kg sc) RV decompensation was confirmed. Then the RV proteome was analyzed using Mass Spectrometry (LC-MSMS). Proteomics revealed 1,277 differentially regulated proteins. Integration of this proteome with our previously published transcriptomic study of RVs harvested from an independent group of rats with MCT-induced PAH revealed 410 common targets, 15 of which were both highly enriched at protein (corrected q -values &lt;0.05) and mRNA level (corrected p-adjust &lt;0.05 ). Most regulated pairs were increased in RVF, including: Atrial natriuretic peptide protein (7.55-fold, transcript = 4.19-fold), Thrombospondin-4 protein (5.56-fold, transcript = 4.4-fold), Periostin (protein = 3.83-fold, transcript = 4.56-fold), Latent transforming growth factor beta binding protein 2 (2.67-fold, transcript = 4.16-fold), Heme oxygenase 1 (4.59-fold, transcript = 2.05-fold), Transforming Growth Factor Beta-1-Induced Transcript 4 Protein (3.82-fold, transcript = 2.1-fold), Transmembrane glycoprotein NMB (3.21-fold, transcript = 2.35-fold), S100 calcium-binding protein A4 (2.43-fold, transcript = 1.93-fold), Collagen XVIII, alpha 1 (2.59-fold, transcript = 1.61-fold), Ankyrin repeat domain 2 (4.04-fold, transcript = 2.49-fold), Procollagen-Lysine 2-Oxoglutarate 5-Dioxygenase 1, (6.89-fold, transcript = 2.3-fold), Tenascin-C (5.18-fold, transcript = 2.53-fold). In contrast, ATPase Na+/K+ Transporting Subunit Alpha 2 3.47 (protein = 3.47-fold, transcript = 2.23-fold) and Glutathione S-Transferase Zeta 1 (protein = 1.97-fold, transcript = 2.38-fold) were downregulated in RVF. A functional analysis of this list of regulated protein/transcript pairs revealed enriched functions include mitochondrial metabolism, cellular respiration and purine metabolism. Our integrated multiomic approach is validated by independent datasets and provides a molecular context for RVF in MCT-induced PAH.

Application of 7.0 T ultra-high-field MRI in evaluating the structure and function of the right ventricle of the heart in rats under a chronic hypoxic environment at high altitude.

BackgroundLong-term exposure to a high-altitude environment with low pressure and low oxygen can cause abnormalities in the structure and function of the heart, in particular the right ventricle. Monitoring the structure and function of the right ventricle is therefore essential for early diagnosis and prognosis of high-altitude heart-related diseases. In this study, 7.0 T MRI is used to detect cardiac structure and function indicators of rats in natural plateau and plain environments.MethodsRats in two groups were raised in different environments from 6 weeks of age for a period of 12 weeks. At 18 weeks of age both groups underwent 7.0 T cardiac magnetic resonance (CMR) scanning. Professional cardiac post-processing software was used to analyze right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV), right ventricular stroke volume (RVSV), right ventricular ejection fraction (RVEF), Right ventricular end-diastolic myocardial mass (RV Myo mass, diast), Right ventricular end-systolic myocardial mass (RV Myo mass, syst), tricuspid valve end-diastolic caliber (TVD), tricuspid valve end-systolic caliber (TVS), right ventricular end-systolic long-axis (RVESL) and right ventricular end-diastolic long-axis (RVEDL). Prior to the CMR scan, blood was collected from the two groups of rats for evaluation of blood indicators. After the scan, the rats were sacrificed and the myocardial tissue morphology observed under a light microscope.ResultsIn the group of rats subject to chronic hypoxia at high altitude for 12 weeks (the plateau group), red blood cell (RBC) count, hemoglobin (HGB) and hematocrit (HCT) increased (P<0.05); RVEDV, RVESV, RVSV, RV Myo mass (diast), RV Myo mass (syst), TVS, RVESL, and RVEDL also increased (P<0.05). Observation of the right ventricle of rats in the plateau group using a light microscope mainly showed a slightly widened myocardial space, myocardial cell turbidity, vacuolar degeneration, myocardial interstitial edema, vascular congestion and a small amount of inflammatory cell infiltration.ConclusionsThe importance of ultra-high-field MRI for monitoring the early stages of rat heart injury has been demonstrated by studying the changes in the structure and function of the right ventricle of rats subject to chronic hypoxia at high altitude over a period of 12 weeks.

Discordant interventricular differences in the excitation‐contraction coupling explained by the lower levels of troponin and Ca 2+ buffering in the right ventricle of rats

The left and right ventricles have distinctive functional characteristics as well as the anatomical differences. However, precise understanding of interventricular differences in the excitation-contraction (E-C) coupling mechanisms and the Ca2+ homeostasis is still lacking. Here we compared the results from the right and left cardiomyocytes (RVCMs and LVCMs) of rats by using whole-cell patch clamp and IonOptix measuring cytosolic Ca2+ ([Ca2+]i) and contractility. RVCMs showed significantly shorter action potential duration (APD), with higher density of transient outward K+ current (Ito) while similar L-type Ca2+ current. However, the triggered [Ca2+]ichange (Ca2+ transient) was not different while the decaying rate of Ca2+ transient was slower in RVCMs. More perplexingly, the sarcomere shortening amplitude (DSL) was smaller and the relaxation speed was slower in RVCMs than LVCMs. The analysis of SERCA activity in situ revealed approximately 50% lower level in RVCMs. Interestingly, the immunoblot analysis revealed lower expression of cardiac troponin complex (cTnC, cTnI and cTnT) in RVCMs. The lower Ca2+ binding cTnC implied smaller Ca2+ buffering capacity (κS), which could be responsible for the similar amplitude of Ca2+-transient despite the shorter APD in RVCMs. In situ analysis using known concentration of fura-2 revealed lower κS in the RVCMs. Introduction of the 1.9 fold Ito, 0.5 fold SERCA, and 0.7 fold cTn into the mathematical model of rat LVCM reproduced the similar Ca2+ transient and the slower Ca2+ decay along with the shorter APD of RVCM. Taken together, we firstly show the lower expression of cTn proteins in the RVCMs, which gives a clue to explain the inter-ventricular difference in the E-C coupling kinetics.

Metabolic remodeling in the right ventricle of rats with severe pulmonary arterial hypertension.

It is generally considered that there is an increase in glycolysis in the hypertrophied right ventricle (RV) during pulmonary hypertension (PH), which leads to a decrease in glucose oxidation through the tricarboxylic acid (TCA) cycle. Although recent studies have demonstrated that fatty acid (FA) and glucose accumulated in the RV of patients with PH, the details of this remain to be elucidated. The purpose of the current study was to assess the metabolic remodeling in the RV of rats with PH using a metabolic analysis. Male rats were treated with the vascular endothelial growth factor receptor blocker SU5416 followed by 3weeks of hypoxic conditions and 5weeks of normoxic conditions (Su/Hx rats). Hemodynamic measurements were conducted, and the RV was harvested for the measurement of metabolites. A metabolomics analysis revealed a decreasing trend in the levels of alanine, argininosuccinic acid and downstream TCA cycle intermediates, including fumaric and malic acid and an increasing trend in branched‑chain amino acids (BCAAs) in Su/Hx rats compared with the controls; however, no trends in glycolysis were indicated. The FA metabolomics analysis also revealed a decreasing trend in the levels of long‑chain acylcarnitines, which transport FA from the cytosol to the mitochondria and are essential for beta‑oxidation. The current study demonstrated that the TCA cycle was less activated because of a decreasing trend in the expression of fumaric acid and malic acid, which might be attributable to the expression of adenylosuccinic acid and argininosuccinic acid. These results suggest that dysregulated BCAA metabolism and a decrease in FA oxidation might contribute to the reduction of the TCA cycle reactions.

Vasoactive Intestinal Peptide Changes the Frequency and Force of Myocardial Contraction in Rats.

We studied the effect of non-selective agonist of VIP receptors of vasoactive intestinal polypeptide in different concentrations on the frequency, force, and duration of isometric contraction of myocardial strips of the right atrium under conditions of spontaneous activity, as well as the force and duration of contractions of the right ventricle in rats. It was found that the agonist produced a positive inotropic and chronotropic effect that depended on its concentration. The maximum effect was observed at vasoactive intestinal peptide concentration of 10-11 M.

Resistance training prevents right ventricle hypertrophy in rats exposed to secondhand cigarette smoke.

Exposure to secondhand cigarette smoke is associated with the development of diverse diseases. Resistance training has been considered one of the most useful tools for patients with pulmonary disease, improving their quality of life. This study aimed to evaluate the effect of resistance training (RT) on the prevention of thickening of the right ventricle wall of rats exposed to secondhand cigarette smoke. Thirty-two Wistar rats were divided into four groups: Control (C), Smoker (S), Exercised (E) and Exercised Smoker (ES). The smoker groups were exposed to the smoke of four cigarettes for 30 min, twice daily, five days a week, for 16 weeks. The exercised groups climbed on a vertical ladder with progressive load, once a day, five days a week, for 16 weeks. The heart, trachea, lung, liver and gastrocnemius muscle were removed for histopathological analysis. Pulmonary emphysema (S and ES vs C and E, P < 0.0001) and pulmonary artery thickness enlargement (S vs C and E, P = 0.003, ES vs C, P = 0.003) were detected in the smoking groups. There was an increase in the right ventricle thickness in the S group compared with all other groups (P < 0.0001). An increase in resident macrophages in the liver was detected in both smoking groups compared with the C group (P = 0.002). Additionally, a relevant reduction of the diameter of the muscle fibers was detected only in ES compared with the C, S and E groups (P = 0.0002), impairing, at least in part, the muscle mass in exercised smoking rats. Therefore, it was concluded that resistance training prevented the increase of thickness of the right ventricle in rats exposed to secondhand cigarette smoke, but it may be not so beneficial for the skeletal muscle of smoking rats.

MiR-1-5p targets TGF-βR1 and is suppressed in the hypertrophying hearts of rats with pulmonary arterial hypertension.

The microRNA miR-1 is an important regulator of muscle phenotype including cardiac muscle. Down-regulation of miR-1 has been shown to occur in left ventricular hypertrophy but its contribution to right ventricular hypertrophy in pulmonary arterial hypertension are not known. Previous studies have suggested that miR-1 may suppress transforming growth factor-beta (TGF-β) signalling, an important pro-hypertrophic pathway but only indirect mechanisms of regulation have been identified. We identified the TGF-β type 1 receptor (TGF-βR1) as a putative miR-1 target. We therefore hypothesized that miR-1 and TGF-βR1 expression would be inversely correlated in hypertrophying right ventricle of rats with pulmonary arterial hypertension and that miR-1 would inhibit TGF-β signalling by targeting TGF-βR1 expression. Quantification of miR-1 and TGF-βR1 in rats treated with monocrotaline to induce pulmonary arterial hypertension showed appropriate changes in miR-1 and TGF-βR1 expression in the hypertrophying right ventricle. A miR-1-mimic reduced enhanced green fluorescent protein expression from a reporter vector containing the TGF-βR1 3'- untranslated region and knocked down endogenous TGF-βR1. Lastly, miR-1 reduced TGF-β activation of a (mothers against decapentaplegic homolog) SMAD2/3-dependent reporter. Taken together, these data suggest that miR-1 targets TGF-βR1 and reduces TGF-β signalling, so a reduction in miR-1 expression may increase TGF-β signalling and contribute to cardiac hypertrophy.

Electrophysiological remodeling of the right ventricle in experimental heart failure of different etiologies

The aim of the study was to evaluate electrophysiological remodeling of the right ventricle in rats in experimental heart failure of different etiologies. Materials and methods. Isadrin-, doxorubicin- and monocrotaline-induced heart failure models were developed. Unipolar epicardial electrograms of the ventricles (256 recording sites) were recorded using a 144-channel system. The cardiac output and pressure in both ventricles of the heart were measured. Activation-recovery intervals were used as an index of duration of local repolarization, and the general and local dispersions of activation-recovery intervals were used as an index of heterogeneity of ventricular repolarization. Results. In all models of heart failure, the following were identified: 1) non-uniform prolongation of repolarization with the greatest elongation at the apex of the right ventricle; 2) an increase in apicobasal differences of repolarization with the greatest change in the right ventricle; 3) an increase in the heterogeneity of the repolarization of the epicardial layer of the ventricles with heterogeneous changes in the local heterogeneity of repolarization and a decrease in the interregional differences in the heterogeneity of the electrophysiological properties of the myocardium; 4) more pronounced changes in the repolarization of the right ventricle than in the repolarization of the left ventricle. Conclusion. Thus, irrespective of the cause of the heart failure, the following changes occur: 1) prolongation of the right ventricular repolarization occurs non-uniformly (mostly due to the apical area), which results in an increase in the right ventricular repolarization heterogeneity; 2) an increase in the heterogeneity of right ventricular repolarization is observed, which causes an increase in the overall heterogeneity of the ventricular epicardial surface.

Salubrinal attenuates right ventricular hypertrophy and dysfunction in hypoxic pulmonary hypertension of rats

The phosphorylation of eukaryotic translation initiation factor 2 alpha (p-eIF2α) is essential for cell survival during hypoxia. The aim of this study was to investigate whether salubrinal, an inhibitor of p-eIF2α dephosphorylation could attenuate pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy in rats exposed to hypobaric hypoxia. PAH of rats was induced by hypobaric hypoxia. Salubrinal supplemented was randomized in either a prevention or a reversal protocol. At the end of the follow-up point, we measured echocardiography, hemodynamics, hematoxylin-eosin and Masson's trichrome stainings. RNA-seq analysis is explored to identify changes in gene expression associated with hypobaric hypoxia with or without salubrinal. Compared with vehicle-treatment rats exposed to hypobaric hypoxia, salubrinal prevented and partly reversed the increase of the mean pulmonary artery pressure and RV hypertrophy. What's more, salubrinal reduced the percentage wall thickness (WT%) of pulmonary artery and RV collagen volume fraction (CVF) in both prevention and reversal protocols. We also found that salubrinal was capable of reducing endoplasmic reticulum stress and oxidative stress. The result of RNA-seq analysis revealed that chronic hypoxia stimulated the differential expression of a series of genes involved in cell cycle regulation and ventricular hypertrophy and so on. Some of these genes could be ameliorated by salubrinal. These results indicate that salubrinal could prevent and reverse well-established RV remodeling, and restore the genes and pathways altered in the right ventricles of rats exposed to hypobaric hypoxia.

SGC–cGMP–PKG pathway stimulation protects the healthy but not the failing right ventricle of rats against ischemia and reperfusion injury

BackgroundTo investigate whether modulation of the sGC–cGMP–PKG pathway protects against ischemia and reperfusion injury in the healthy and the failing right ventricle (RV). MethodsHearts from male Wistar rats with a healthy RV (n=39) or a hypertrophic and failing RV induced by pulmonary trunk banding (n=57) were isolated and perfused in a pressure-controlled modified Langendorff setup. The isolated hearts were randomized to control, ischemic preconditioning (IPC, 2×5min of global ischemia), a phosphodiesterase-5 (PDE5) inhibitor vardenafil (66nM) alone and in combination with a cGMP-dependent protein kinase (PKG) blocker KT 5823 (1μM). Failing hearts were exposed to the same protocols and to soluble guanylate cyclase stimulation/activation, and phosphodiesterase 9 inhibition. All interventions were followed by 40min of global ischemia and 120min of reperfusion. The effects on the RV were evaluated by measurement of the infarct size/area-at-risk ratio (IS/AAR). ResultsIn healthy hearts, IPC and pharmacological preconditioning with vardenafil reduced RV infarct size. PKG blockade by KT-5823 did not alter infarct size per se but abolished the cardioprotective effect of vardenafil. In the hypertrophic and failing hearts, none of the conditioning strategies altered RV infarct size. ConclusionPDE-5 inhibition by vardenafil protects the healthy right ventricle against ischemia and reperfusion injury by a PKG dependent mechanism. Neither ischemic preconditioning nor pharmacologic stimulation of the sGC–cGMP–PKG pathway induces cardioprotection in the hypertrophic and failing RV.

Inotropic Effect of Dopamine on Rat Heart during Postnatal Ontogeny

We studied the effect of dopamine in concentrations of 10(-9), 10(-8), 10(-7), 10(-6), and 10(-5) M on contraction strength of isolated myocardial strips from the right atrium and right ventricle of rats aging 21, 42, 56, and 100 days. Dopamine in a concentration of 10(-9) M had a positive inotropic effect in rats of various ages. Increasing the concentration of dopamine to 10(-7)-10(-5) M was accompanied by a negative inotropic effect on the heart.

Microtubule proliferation in right ventricular myocytes of rats with monocrotaline-induced pulmonary hypertension

Microtubules are components of the cardiac cytoskeleton that can proliferate in response to pressure-overload in animal and human heart failure. We wished to test whether there was a proliferation of the microtubule cytoskeleton in the right ventricle of rats with pulmonary hypertension induced by monocrotaline (MCT) and whether this contributed to contractile dysfunction. Male Wistar rats were injected with 60mg/kg of MCT in saline or an equivalent volume of saline (CON). MCT produced clinical signs of heart failure within 4weeks of injection. Expression of right ventricular mRNA for α-tubulin was measured by real-time reverse transcription polymerase chain reaction. Free and polymerised fractions of β-tubulin protein were assessed using Western blot analysis and immunofluorescence microscopy was used to assess tyrosinated and acetylated (stabilized) microtubules. Right ventricular myocyte contraction was measured in response to the microtubule de-polymeriser colchicine (10μmol/l for at least 1h). Compared to CON, in MCT right ventricles there was a small but statistically significant increase in the expression of mRNA for α-tubulin (P<0.001); total (P<0.05) and polymerised fraction (P<0.01) of β-tubulin protein and level of acetylated tubulin (P<0.01). However colchicine treatment did not increase the contraction of MCT myocytes (P>0.05) or affect their response to increased stimulation frequency. Our observations support the hypothesis that microtubule proliferation is a common response to pulmonary hypertension in failing right ventricles but suggest that the effect this has on contraction depends upon the specific experimental or clinical conditions that prevail and the subsequent level of microtubule proliferation.

Pulmonary Hypertension-Induced GATA4 Activation in the Right Ventricle

The major cause of death among pulmonary hypertension patients is right heart failure, but the biology of right heart is not well understood. Previous studies showed that mechanisms of the activation of GATA4, a major regulator of cardiac hypertrophy, in response to pressure overload are different between left and right ventricles. In the left ventricle, aortic constriction triggers GATA4 activation via posttranslational modifications without influencing GATA4 expression, while pulmonary artery banding enhances GATA4 expression in the right ventricle. We found that GATA4 expression can also be increased in the right ventricle of rats treated with chronic hypoxia to induce pulmonary hypertension and investigated the mechanism of increased GATA4 expression. Examination of Gata4 promoter revealed that CCAAT box plays an important role in gene activation, and hypoxic pulmonary hypertension promoted the binding of CCAAT-binding factor/nuclear factor-Y (CBF/NF-Y) to CCAAT box in the right ventricle. We found that CBF/NF-Y forms a complex with annexin A1, which inhibits DNA binding activity. In response to hypoxic pulmonary hypertension, annexin A1 gets degraded, resulting in CBF/NF-Y-dependent activation of Gata4 gene transcription. The right ventricle contains a higher level of CBF/NF-Y compared to the left ventricle, and this may allow for efficient activation in response to annexin A1 degradation. Signaling via iron-catalyzed protein oxidation mediates hypoxic pulmonary hypertension-induced annexin A1 degradation, Gata4 gene transcription, and right ventricular hypertrophy. These results establish a right heart-specific signaling mechanism in response to pressure overload, which involves metal-catalyzed carbonylation and degradation of annexin A1 that liberates CBF/NF-Y to activate Gata4 gene transcription.

Downregulation of oxytocin receptors in right ventricle of rats with monocrotaline‐induced pulmonary hypertension

pulmonary hypertension (PH) in the rat leads to right ventricular (RV) hypertrophy, inflammation and increased natriuretic peptide (NP) levels in plasma and RV. Because the release of nitric oxide (NO) and atrial natriuretic peptide (ANP) is a function of the oxytocin receptor (OTR), we examined the effect of PH on gene and protein expression of OTR, NP (A, atrial; B, brain) and receptors (NPRs), nitric oxide synthases (NOS), interleukin (IL)-1β, IL-6 and tumour necrosis factor-α in the hypertrophied RV in a model of PH. RV hypertrophy was induced in male Sprague-Dawley rats with monocrotaline (MCT; 60 mg kg(-1) ) and was confirmed by the presence of an increased RV weight and RV-to-[left ventricle (LV) and septum] ratio. in the RV of MCT-treated rats, a approximately 40% reduction in OTR mRNA and protein was observed compared with the RV of control rats. This reduction was associated with increased transcripts of ANP and BNP in both ventricles and a corresponding increase in NP receptor mRNA expression for receptors A, B and C. Protein expression of inducible NOS was increased in the RV, whereas endothelial NOS transcripts were increased only in the LV of MCT-treated rats. In the RV of MCT-treated rats, downregulation of OTR was also associated with increased mRNA expression of IL-1β and IL-6. our results show that downregulation of the OTR in the RV of MCT-treated rats is associated with increased expression of NP and their receptors as well as IL-1β and IL-6. This reduction in OTR in RV myocardium may have an impact on cardiac function in the MCT-induced model of PH.

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress

To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8 degrees C for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85%), FLU (4.47%) and IHF (8.4%) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4%) group showed mitochondrial edema and lysis in cristae. The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.

β,γ-Methylene ATP but Not α,β-Methylene ATP Mimicsthe Inhibitory Effect of ATP on Ventricular Automaticity

Abstract: The effects of α,β- and β,γ-methylene ATP on ventricular automaticity induced by local injury in the right ventricle of rats pretreated with reserpine, were investigated and compared with the effects of ATP and adenosine. β,γ-Methylene ATP but not α,β-methylene ATP mimicked the inhibitory effect of both ATP and adenosine on the spontaneous automaticity. In low concentrations, adenosine was more effective than ATP. α,β-Methylene ATP caused little or no effect on ventricular automaticity. The results suggest that the effect of ATP might depend on its hydrolysis into AMP/adenosine.

Effects of angiotensin I-converting enzyme inhibitor and angiotensin II type 1 receptor blocker on the right ventricular sarcoglycans and dystrophin after left coronary artery ligation

We examined the effects of trandolapril and candesartan on changes in the levels of sarcoglycans and dystrophin in the right ventricle of rats with the left coronary artery ligation. Hemodynamic and morphological alterations suggested the development of hypertrophy of the right ventricle and chronic heart failure by the 8th week. By the end of the 8th week, α- and β-sarcoglycans and dystrophin were decreased. Increases in μ- and m-calpains in the hypertrophied right ventricle were associated with an elevation of casein-proteolytic activity in the cytosolic fraction. Oral administration of 3 mg/kg/day trandolapril or 1 mg/kg/day candesartan from the 2nd to 8th week after the left coronary artery ligation attenuated decreases in α-sarcoglycan and dystrophin and reduced the increased proteolytic activity. The results suggest that attenuation of decreases in sarcoglycans and dystrophin is a possible mechanism underlying trandolapril- and candesartan-mediated improvement of structural and functional alterations of the right ventricle in the coronary artery-ligated rat.