natriuretic-peptide--brain and Hypertrophy--Right-Ventricular

Topics: Aging; Animals; Biomarkers; Cardiovascular Diseases; Diagnostic Imaging; Dogs; Fetal Heart; Heart Function Tests; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Myocardial Contraction; Natriuretic Peptide, Brain; Pulmonary Artery; Tricuspid Valve; Ventricular Dysfunction, Right; Ventricular Function; Ventricular Function, Right

B-type natriuretic Peptide (BNP) is elevated in conditions with ventricular volume and pressure overload. The physiological, diagnostic and therapeutic role of BNP in right ventricular (RV) dysfunction and pulmonary arterial hypertension (PAH) are reviewed in this article. BNP levels can be used to differentiate between breathless patients with a respiratory disease and those with PAH. BNP has been shown to correlate with mean pulmonary arterial pressure and pulmonary vascular resistance in patients with PAH, whether primary or secondary. BNP is also a predictor of mortality in patients with primary pulmonary hypertension. These are important clinical implications in that a non-invasive blood test may be used to identify patients who require more invasive procedures (such as cardiac catheterization). There is increasing evidence that BNP or NT-proBNP measurements may also be used to guide therapy (e.g. pulmonary vasorelaxants) in PAH. Enhancement of the natriuretic peptide pathway has been shown to reduce cardiac hypertrophy and PAH and hence, there may be therapeutic potential via recombinant BNP or neutral endopeptidase inhibitors in RV dysfunction and PAH.

Topics: Fibrosis; Heart Ventricles; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Peptide; Vasodilation; Ventricular Dysfunction, Right

Right ventricular dilatation in the setting of acute pulmonary embolism is associated with an adverse prognosis. Treatment with a pulmonary vasodilator has never been studied systematically. We evaluated the effect of epoprostenol on right ventricular diameter and function in patients with acute pulmonary embolism and right ventricular dilatation.. In a randomized, single-blind study, 14 patients with acute pulmonary embolism received epoprostenol or placebo infusion for 24 hours on top of conventional treatment. Effects on right ventricular end-diastolic diameter, systolic pulmonary artery pressure, right ventricle fractional area change and tricuspid annular plane systolic excursion were assessed by serial echocardiography. Furthermore Troponin T and NT-proBNP were measured serially.. Compared to placebo, epoprostenol was associated with a relative change from baseline in right ventricular end-diastolic diameter of +2% after 2.5 hours and -8% after 24 hours. Epoprostenol did not have a significant effect on systolic pulmonary artery pressure, right ventricular fractional area change and tricuspid annular plane systolic excursion, nor on biochemical parameters.. In patients with acute pulmonary embolism and right ventricular overload, treatment with epoprostenol did not improve right ventricular dilatation or any other measured variables of right ventricular overload.. URL: NCT01014156Medical ethical committee: Medisch-ethische toetsingscommissie (METc) from the VUmc (free university medical centre).

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; Echocardiography, Doppler; Epoprostenol; Female; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Single-Blind Method; Troponin T; Ventricular Dysfunction, Right

In animal models of pulmonary hypertension, simvastatin has been shown to reduce pulmonary artery pressure and induce regression of associated right ventricular (RV) hypertrophy.. To assess the therapeutic value of simvastatin in patients with pulmonary arterial hypertension (PAH).. Forty-two patients with PAH were randomized to receive either simvastatin (80 mg/d) or placebo in addition to current care for 6 months, and thereafter offered open-label simvastatin. The primary outcome was change in RV mass, assessed by cardiac magnetic resonance (CMR).. At 6 months, RV mass decreased by 5.2 +/- 11 g in the statin group (P = 0.045) and increased 3.9 +/- 14 g in the placebo group. The treatment effect was -9.1 g (P = 0.028). N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels decreased significantly in the statin group (-75 +/- 167 fmol/ml; P = 0.02) but not the placebo group (49 +/- 224 fmol/ml; P = 0.43; overall treatment effect -124 fmol/ml; P = 0.041). There were no significant changes in other outcome measures (including 6-minute walk test, cardiac index, and circulating cytokines). From 6 to 12 months, both RV mass and NT-proBNP increased toward baseline values in 16 patients on active treatment who continued with simvastatin but remained stable in 18 patients who switched from placebo to simvastatin. Two patients required a reduction in dose but not cessation of simvastatin.. Simvastatin added to conventional therapy produces a small and transient early reduction in RV mass and NT-proBNP levels in patients with PAH, but this is not sustained over 12 months.

Topics: Adult; Aged; Antihypertensive Agents; Double-Blind Method; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Simvastatin; Ultrasonography; Young Adult

Right ventricular (RV) hypertrophy and further heart failure are major co-morbidities, resulting in the premature death of patients with hypoxic pulmonary hypertension (HPH). The regulatory effects of kallikrein-related peptidase (KLK) family members on cardiac function have been extensively studied. However, to the best of the authors' knowledge, the regulatory effects of KLK8 on RV hypertrophy caused by HPH have yet to be reported. The aim of the present study was to assess KLK8 expression in the RV tissue of HPH-modeled rats, and to further explore the effects and underlying mechanism of KLK8 in regulating the hypertrophy of hypoxia-induced H9c2 cardiomyocytes. In HPH model rats, increases in the right ventricle hypertrophy index, the right ventricular systolic pressure, cardiac output, as well as pulmonary artery wall thickness were observed. Western blot analysis revealed that KLK8 expression and MAPK/p53 signaling activity were enhanced in the RVs of rats in an RV HPH rat model. In hypoxia-induced H9c2 cardiomyocytes, KLK8 overexpression promoted cardiomyocyte hypertrophy, whereas KLK8 silencing showed the opposite results. KLK8 overexpression increased the expression levels of ventricular hypertrophy markers, including atrial natriuretic peptide, brain natriuretic peptide and myosin heavy chain 7, which were blocked upon addition of the p38 MAPK inhibitor, SB202190. Conversely, KLK8 silencing caused a decrease in the expression levels of the ventricular hypertrophy markers, which were further reduced via inhibition of the p38 MAPK/p53 signaling pathway. Taken together, the results of the present study have shown that KLK8 may subtly regulate RV hypertrophy, and therefore KLK8 may be a promising therapeutic target for treating HPH-induced RV hypertrophy.

Topics: Animals; Atrial Natriuretic Factor; Hypertrophy, Right Ventricular; Hypoxia; Kallikreins; Myosin Heavy Chains; Natriuretic Peptide, Brain; p38 Mitogen-Activated Protein Kinases; Rats; Serine Endopeptidases; Signal Transduction; Tumor Suppressor Protein p53

Pulmonary arterial hypertension (PAH) is more prevalent in females. Paradoxically, female patients have better right ventricular (RV) function and higher survival rates than males. However, the effects of 17β-estradiol (E2) on RV function in PAH has not been studied. Twenty-four male rats were exposed to monocrotaline (MCT) to induce experimental PAH, while treated with E2 or vehicle respectively. Together with eight control rats, thirty-two rats were examined by echocardiography 4 weeks after drug administration. Echocardiographic measurement of RV function included: tricuspid annular plane systolic excursion (TAPSE), RV index of myocardial performance (RIMP), RV fractional area change (RVFAC) and tricuspid annular systolic velocity (s'). RV free wall longitudinal strain (RVLS

Topics: Animals; Biomarkers; Disease Models, Animal; Echocardiography; Estradiol; Fibrosis; Heart Ventricles; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Natriuretic Peptide, Brain; Rats, Sprague-Dawley; Time Factors; Ventricular Dysfunction, Right; Ventricular Function, Right; Ventricular Remodeling

Persistent pulmonary hypertension of the newborn (PPHN) is a life‑threatening disease that is commonly observed in the neonatal intensive care unit. PPHN is pathologically characterized by pulmonary vascular remodeling and, in particular, pulmonary artery smooth muscle cell (PASMC) proliferation. Decreased expression levels of peroxisome proliferator‑activated receptor γ (PPAR‑γ), which is a member of the nuclear receptor hormone superfamily, in combination with elevated expressions of transient receptor potential cation channel, subfamily C, member 1 (TRPC1) and TRPC6 contributes to the PASMC proliferation and excessive pulmonary vascular remodeling in adult pulmonary hypertension (PH). Whether PPAR‑γ, TRPC1 and TRPC6 affect the development of vascular remodeling in PPHN model rats remains unknown. The aim of the present study was to investigate the roles of PPAR‑γ, TRPC1 and TRP6 on the pathogenesis of PPHN in rats. The rat model of PPHN was established by exposure to hypoxic conditions and indomethacin treatment. Lung tissues, hearts and blood from PPHN model and Control rats were collected and examined. Parameters, including the percentage of medial wall thickness (WT %), the percentage of medial wall area (WA %), right ventricular hypertrophy (RVH) and the plasma concentration of B‑type natriuretic peptide (BNP) were used to estimate the development of PPHN. The expression levels of PPAR‑γ, TRPC1 and TRPC6 in lung tissues were detected by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. Significant increases were observed in the WT %, WA %, RVH and plasma BNP in the PPHN group compare with the Control group (P<0.01). In addition, the mRNA and protein expression levels of PPAR‑γ were markedly downregulated (P<0.05 vs. Control). In the PPHN group, the protein expression levels of TRPC1 and TRPC6 were higher compared to the control group; however, there was no difference in the mRNA expression levels (P>0.05). In conclusion, the present study successfully established a PPHN rat model, and the altered expressions of PPAR‑γ, TRPC1 and TRPC6 in the pulmonary artery located in the lungs of newborn rats with PPHN suggested that these proteins may be important mediators of PPHN.

Topics: Animals; Animals, Newborn; Disease Models, Animal; Female; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung; Natriuretic Peptide, Brain; PPAR gamma; Protein Transport; Rats; Rats, Sprague-Dawley; RNA, Messenger; TRPC Cation Channels; Vascular Remodeling

Topics: Aorta; Echocardiography; Female; Heart Defects, Congenital; Heart Septal Defects, Ventricular; Hemodynamics; Humans; Hypertrophy, Right Ventricular; Imaging, Three-Dimensional; Magnetic Resonance Angiography; Middle Aged; Natriuretic Peptide, Brain; Palliative Care; Peptide Fragments; Pulmonary Atresia; Tomography, X-Ray Computed

Pulmonary arterial hypertension (PAH) is a fatal disease with limited therapeutic options. Pathophysiological changes comprise obliterative vascular remodelling of small pulmonary arteries, elevated mean pulmonary arterial systolic pressure (PASP) due to elevated resistance of pulmonary vasculature, adverse right ventricular remodelling, and heart failure. Recent findings also indicate a role of increased inflammation and insulin resistance underlying the development of PAH. We hypothesized that treatment of this condition with the peroxisome proliferator-activated receptor-γ (PPARγ) activator pioglitazone, known to regulate the expression of different genes addressing insulin resistance, inflammatory changes, and vascular remodelling, could be a beneficial approach. PAH was induced in adult rats by a single subcutaneous injection of monocrotaline (MCT). Pioglitazone was administered for 2 weeks starting 3 weeks after MCT-injection. At day 35, hemodynamics, organ weights, and -indices were measured. We performed morphological and molecular characterization of the pulmonary vasculature, including analysis of the degree of muscularization, proliferation rates, and medial wall thickness of the small pulmonary arteries. Furthermore, markers of cardiac injury, collagen content, and cardiomyocyte size were analyzed. Survival rates were monitored throughout the experimental period. Pioglitazone treatment improved survival, reduced PASP, muscularization of small pulmonary arteries, and medial wall thickness. Further, MCT-induced right ventricular hypertrophy and fibrosis were attenuated. This was accompanied with reduced cardiac expression of brain natriuretic peptide, as well as decreased cardiomyocyte size. Finally, pulmonary macrophage content and osteopontin gene expression were attenuated. Based on the beneficial impact of pioglitazone, activation of PPARγ might be a promising treatment option in PAH.

Topics: Animals; Arterial Pressure; Cardiovascular Agents; Disease Models, Animal; Fibrosis; Heart Ventricles; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Macrophages, Alveolar; Male; Monocrotaline; Myocytes, Cardiac; Natriuretic Peptide, Brain; Osteopontin; Pioglitazone; PPAR gamma; Pulmonary Artery; Rats, Sprague-Dawley; Thiazolidinediones; Vascular Remodeling; Ventricular Function, Right; Ventricular Remodeling

Limited therapies exist for patients with congenital heart disease (CHD) who develop right ventricular (RV) dysfunction. Bone marrow-derived mesenchymal stem cells (MSCs) have not been evaluated in a preclinical model of pressure overload, which simulates the pathophysiology relevant to many forms of CHD. A neonatal swine model of RV pressure overload was utilized to test the hypothesis that MSCs preserve RV function and attenuate ventricular remodeling. Immunosuppressed Yorkshire swine underwent pulmonary artery banding to induce RV dysfunction. After 30 min, human MSCs (1 million cells, n = 5) or placebo (n = 5) were injected intramyocardially into the RV free wall. Serial transthoracic echocardiography monitored RV functional indices including 2D myocardial strain analysis. Four weeks postinjection, the MSC-treated myocardium had a smaller increase in RV end-diastolic area, end-systolic area, and tricuspid vena contracta width (P < 0.01), increased RV fractional area of change, and improved myocardial strain mechanics relative to placebo (P < 0.01). The MSC-treated myocardium demonstrated enhanced neovessel formation (P < 0.0001), superior recruitment of endogenous c-kit+ cardiac stem cells to the RV (P < 0.0001) and increased proliferation of cardiomyocytes (P = 0.0009) and endothelial cells (P < 0.0001). Hypertrophic changes in the RV were more pronounced in the placebo group, as evidenced by greater wall thickness by echocardiography (P = 0.008), increased cardiomyocyte cross-sectional area (P = 0.001), and increased expression of hypertrophy-related genes, including brain natriuretic peptide, β-myosin heavy chain and myosin light chain. Additionally, MSC-treated myocardium demonstrated increased expression of the antihypertrophy secreted factor, growth differentiation factor 15 (GDF15), and its downstream effector, SMAD 2/3, in cultured neonatal rat cardiomyocytes and in the porcine RV myocardium. This is the first report of the use of MSCs as a therapeutic strategy to preserve RV function and attenuate remodeling in the setting of pressure overload. Mechanistically, transplanted MSCs possibly stimulated GDF15 and its downstream SMAD proteins to antagonize the hypertrophy response of pressure overload. These encouraging results have implications in congenital cardiac pressure overload lesions.

Topics: Animals; Disease Models, Animal; Humans; Hypertrophy, Right Ventricular; Mesenchymal Stem Cell Transplantation; Myosin Heavy Chains; Myosin Light Chains; Natriuretic Peptide, Brain; Swine; Ventricular Dysfunction, Right; Ventricular Pressure; Ventricular Remodeling

Pediatric pulmonary arterial hypertension (PAH) presents certain specific features. In this specific age group, experimental models to study the pathophysiology of PAH are lacking. To characterize hemodynamic, morphometric, and histological progression as well as the expression of neurohumoral factors and regulators of cardiac transcription in an infantile model of PAH induced by monocrotaline (MCT), eight-day-old Wistar rats were randomly injected with MCT (30 mg/kg, sc, n = 95) or equal volume of saline solution (n = 92). Animals were instrumented for biventricular hemodynamic recording 7, 14, and 21 days after MCT, whereas samples were collected at 1, 3, 7, 14, and 21 days after MCT. Different time point postinjections were defined for further analysis. Hearts and lungs were collected for morphometric characterization, assessment of right- and left-ventricle (RV and LV) cardiomyocyte diameter and collagen type-I and type-III ratio, RV collagen volume fraction, and pulmonary vessels wall thickness. mRNA quantification was undertaken for brain natriuretic peptide (BNP), endothelin-1 (ET-1), and for cardiac transcription regulators (HOP and Islet1). Animals treated with MCT at the 8th day of life presented RV hypertrophy since day 14 after MCT injection. There were no differences on the RV collagen volume fraction or collagen type-I and type-III ratio. Pulmonary vascular remodelling and PAH were present on day 21, which were accompanied by an increased expression of BNP, ET-1, HOP, and Islet1. The infantile model of MCT-induced PAH can be useful for the study of its pathophysiology and to test new therapeutic targets in pediatric age group.

Topics: Animals; Animals, Newborn; Collagen Type I; Collagen Type III; Disease Models, Animal; Endothelin-1; Female; Heart; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung; Male; Monocrotaline; Myocytes, Cardiac; Natriuretic Peptide, Brain; Pyrrolizidine Alkaloids; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Transcription Factors

Risk factors for obstructive sleep apnea (OSA) and the development of subsequent cardiovascular (CV) complications differ by sex. We hypothesize that the relationship between OSA and high-sensitivity troponin T (hs-TnT), cardiac structure, and CV outcomes differs by sex.. Seven hundred fifty-two men and 893 women free of CV disease participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies were included. All participants (mean age, 62.5 ± 5.5 years) underwent polysomnography and measurement of hs-TnT. OSA severity was defined by using established clinical categories. Subjects were followed for 13.6 ± 3.2 years for incident coronary disease, heart failure, and CV and all-cause mortality. Surviving subjects underwent echocardiography after 15.2 ± 0.8 years. OSA was independently associated with hs-TnT among women (P=0.03) but not in men (P=0.94). Similarly, OSA was associated with incident heart failure or death in women (P=0.01) but not men (P=0.10). This association was no longer significant after adjusting for hs-TnT (P=0.09). Among surviving participants without an incident CV event, OSA assessed in midlife was independently associated with higher left ventricle mass index only among women (P=0.001).. Sex-specific differences exist in the relationship between OSA and CV disease. OSA, assessed in midlife, is independently associated with higher levels of concomitantly measured hs-TnT among women but not men, in whom other comorbidities associated with OSA may play a more important role. During 13-year follow-up, OSA was associated with incident heart failure or death only among women, and, among those without an incident event, it was independently associated with left ventricular hypertrophy only in women.

Topics: Aged; Biomarkers; C-Reactive Protein; Comorbidity; Coronary Disease; Death Certificates; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Hypertrophy, Left Ventricular; Hypertrophy, Right Ventricular; Male; Middle Aged; Mortality; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Prospective Studies; Severity of Illness Index; Sex Factors; Sleep Apnea, Obstructive; Troponin T; Ultrasonography; United States

To be able to design goal-oriented treatment strategies in paediatric pulmonary arterial hypertension (PAH), we aimed to identify treatment goals by investigating the prognostic value of treatment-induced changes in noninvasive predictors of transplant-free survival. 66 consecutive, treatment-naïve paediatric PAH patients in the Dutch National Network for Paediatric Pulmonary Hypertension who started taking PAH-targeted drugs between January 2000 and April 2013 underwent prospective, standardised follow-up. Clinical, biochemical and echocardiographic measures were longitudinally collected at treatment initiation and follow-up, and their respective predictive values for transplant-free survival were assessed. Furthermore, the predictive values of treatment-induced changes were assessed. From the identified set of baseline predictors, the variables World Health Organization functional class (WHO-FC), N-terminal pro-brain natriuretic peptide (NT-proBNP) and tricuspid annular plane systolic excursion (TAPSE) were identified as follow-up predictors in which treatment-induced changes were associated with survival. Patients in whom these variables improved after treatment showed better survival (p<0.002). Therefore, WHO-FC, NT-proBNP and TAPSE are not only predictors of transplant-free survival in paediatric PAH but can also be used as treatment goals, as treatment-induced improvements in these variables are associated with improved survival. The identification of these variables allows for the introduction of goal-oriented treatment strategies in paediatric PAH.

Topics: Adolescent; Cardiac Catheterization; Child; Child, Preschool; Cohort Studies; Disease Progression; Echocardiography; Endothelin Receptor Antagonists; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung Transplantation; Male; Natriuretic Peptide, Brain; Patient Care Planning; Peptide Fragments; Phosphodiesterase 5 Inhibitors; Prospective Studies; Prostaglandins I; Pulmonary Wedge Pressure; Survival Analysis; Tricuspid Valve Insufficiency

There is considerable interest in the pleiotropic effects of statins and their potential role in the treatment of pulmonary hypertension. Previous experimental findings indicate that a combination of lipophilic statins with phosphodiesterase type-5 inhibitor, sildenafil, can offer preventive effects on rat monocrotaline-induced pulmonary hypertension. The present study is aimed to assess whether therapeutic regimen provides any benefits. Seven days after pulmonary hypertension induction, hydrophilic rosuvastatin and sildenafil were given for 14 days to male Wistar outbred rats. Right ventricular pressure, right ventricle mass and three biomarkers were evaluated after 21 days: brain natriuretic peptide, high-density lipoprotein cholesterol and vascular endothelial growth factor. The present study demonstrates that administration of hydrophilic statin with sildenafil results in reduction of pulmonary vascular remodeling and right ventricular pressure. The results of biochemical measurements may suggest that statins play a positive role in right ventricle function or the process of angiogenesis in pulmonary hypertension development.

Topics: Animals; Antihypertensive Agents; Arterial Pressure; Biomarkers; Cholesterol, HDL; Disease Models, Animal; Drug Therapy, Combination; Fluorobenzenes; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Male; Monocrotaline; Natriuretic Peptide, Brain; Phosphodiesterase 5 Inhibitors; Piperazines; Pulmonary Artery; Purines; Pyrimidines; Rats, Wistar; Rosuvastatin Calcium; Sildenafil Citrate; Sulfonamides; Time Factors; Vascular Endothelial Growth Factor A; Vascular Remodeling; Vasodilator Agents; Ventricular Function, Right; Ventricular Pressure

Pulmonary fibrosis is often complicated by pulmonary hypertension. Statins reduce fibroblast activity in vitro and pulmonary hypertension in vivo. We investigated whether Simvastatin exerts beneficial effects on pulmonary fibrosis and pulmonary hypertension in Bleomycin-treated rats in vivo.. Rats were randomly assigned to controls, Bleomycin, Bleomycin plus Simvastatin from day 1 to 28 and Bleomycin plus Simvastatin from day 13 to 28. 28 days after Bleomycin instillation, right ventricular systolic pressure (RVSP), right ventricular mass (RV/(LV+S)), right ventricular and circulating brain natriuretic peptide (BNP) levels were determined to assess pulmonary hypertension. Pulmonary hydroxyproline content (HPC), pulmonary connective tissue growth factor (CTGF) transcription and lung compliance (LC) were analysed to characterize pulmonary fibrosis. Exercise capacity was determined by treadmill tests.. Compared with controls, Bleomycin increased RVSP, RV/(LV+S), BNP levels, HPC and CTGF transcription and decreased LC significantly. Simvastatin administered from day 1 to 28 normalized all these parameters. Simvastatin administered from day 13 to 28 had no effect on HPC and LC, but reduced RV/(LV+S) significantly and induced a strong trend to lower RVSP and BNP levels. Exercise capacity was reduced by Bleomycin. Simvastatin significantly improved exercise intolerance in both treatment groups.. Simvastatin prevents the development of pulmonary fibrosis, but fails to attenuate already established pulmonary fibrosis. In contrast, it ameliorates pulmonary hypertension and thereby exercise capacity in the prevention and the treatment group regardless of its effects on pulmonary fibrosis. Whether statins are a treatment option in humans with pulmonary fibrosis needs to be investigated by further study.

Topics: Animals; Bleomycin; Hydroxyproline; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Lung Compliance; Male; Motor Activity; Natriuretic Peptide, Brain; Pulmonary Fibrosis; Random Allocation; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Simvastatin

We sought to investigate the experimental therapeutic effects and mechanisms of iptakalim, a new adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) opener, on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and right heart ventricle remodeling in rats.. Rats were injected with a single dose (50 mg/kg, ip) of MCT and given iptakalim (1, 3, and 9 mg/kg·per d, orally [po]) or saline for 28 days. The hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis.. Treatment with iptakalim at daily oral doses of 1, 3, and 9 mg/kg from the day of MCT injection attenuated the high right ventricle systolic pressure (RVSP) and the increased weight ratio of right ventricle (RV) to left ventricle (LV) plus septum (S) (RV/(LV+S)), decreased heart rate (HR) and decreased mean arterial pressure (MAP), inhibited the RV myocardial tissue cell apoptosis, and the RV myocardial cell B-type natriuretic peptide (BNP) protein expression. Iptakalim also decreased the serum levels of nitric oxide (NO), endothelin 1 (ET-1), BNP, and the levels of NO, ET-1, and tumor necrosis factor-alpha (TNF-α) in the lung tissue.. These results indicate that iptakalim prevents MCT-induced PAH and RV remodeling and its mechanisms are related to inhibiting the pathological increases in NO, ET-1, BNP, and TNF-α, and Iptakalim may be a promising candidate for the treatment of PAH.

Topics: Animals; Endothelin-1; Familial Primary Pulmonary Hypertension; Hemodynamics; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; KATP Channels; Lung; Male; Monocrotaline; Natriuretic Peptide, Brain; Nitric Oxide; Propylamines; Rats; Rats, Wistar

Improved medical techniques have allowed most women with repaired tetralogy of Fallot (TOF) to reach childbearing age. The predictors of adverse events and the effects of pregnancy on cardiac function have not been clearly described in these patients.. In the present study we retrospectively reviewed 40 deliveries in 25 patients with repaired TOF. There were 23 patients in New York Heart Association (NYHA) class I, and 2 in classes II-III before pregnancy. The mean age at delivery was 29.1 years and the mean gestational period was 37.8 weeks. Seven pregnancies (17.5%) in 7 patients were complicated with cardiac events such as a decline in NYHA class and arrhythmia. History of ablation and the baseline cardiothoracic ratio on chest radiography were predictors of adverse events. Peak plasma brain natriuretic peptide (BNP) level after the second trimester was higher in patients with cardiac events. Left ventricular size and contraction did not change from before to after pregnancy, but the right ventricle was enlarged at 6 months after delivery.. Many of the pregnancies in women with repaired TOF were successful. However, careful management is required for some patients and the BNP level may be a useful marker to identify these patients. Because the right heart tended to be enlarged in the late postpartum period, pregnancy may also affect the long-term prognosis of patients with repaired TOF.

Topics: Adult; Biomarkers; Cardiac Surgical Procedures; Chi-Square Distribution; Female; Gestational Age; Humans; Hypertrophy, Right Ventricular; Japan; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy Outcome; Retrospective Studies; Risk Assessment; Risk Factors; Tetralogy of Fallot; Time Factors

We studied relationship between structure-functional parameters of left and right cardiac chambers and N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 118 patients with arterial hypertension (AH) (35 men, 83 women) and 17 healthy volunteers. Methods comprised 24-hour arterial pressure monitoring (APM), two-dimensional echocardiography (echoCG), Doppler echoCG, and tissue echoCG of mitral and tricuspid atrioventricular annuli, treadmill test, 6-min walk test, and measurement of NT-proBNP level in blood plasma. In patients with AH blood plasma NT-proBNP level was significantly higher than in a group of healthy persons of similar age. Elevation of this biochemical marker was accompanied by significant change of characteristics of remodeling of left and right parts of the heart, abnormalities of left ventricular diastolic function according to transmitral blood flow, disturbances of left ventricular diastolic and systolic function according to tissue Doplerography data. Comparative analysis of structure-functional parameters of the heart and NT-proBNP level in patients with AH allowed to reveal more significant changes of parameters of diastolic and systolic remodeling, local and global diastolic and systolic left ventricular function in patients with NT-proBNP levels more than 306 mol/ml. Factors determining NT-proBNP level in patients with AH were age, free right ventricular wall thickness, and body mass index.

Topics: Adult; Biomarkers; Body Mass Index; Echocardiography, Doppler; Exercise Test; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Right Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Research Design; Statistics as Topic; Ventricular Dysfunction; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

Topics: Acute Disease; Adult; Aged; Biomarkers; Female; Fibrin Fibrinogen Degradation Products; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Pulmonary Embolism; ROC Curve; Tomography, X-Ray Computed; Troponin T

Plasma B-type natriuretic peptide (BNP) levels are closely related to symptoms in left ventricle (LV) systolic heart failure, although marked regarding heterogeneity levels among subjects are reported.. To assess the influence of right ventricle on plasma BNP in the patients with different grades of its overload secondary to severe mitral valve stenosis (MVS).. Plasma BNP was evaluated in MVS patients (n = 27) before valve replacement and during follow-up (FUV) 401 ± 42 days after operation.. Initial examination showed severe MVS (0.9 ± 0.2 cm²), left atrial enlargement (LAI 30 ± 4.5 mm m⁻²), right ventricle diastolic dilatation (RVDI 16 ± 3.6 mm m⁻²), normal LV size/function and elevated BNP levels (166 ± 137 pg ml⁻¹). FUV examination revealed a significant reduction in LAI (27 ± 2.2 mm m⁻²), RVDI (14 ± 1.6 mm m⁻²) and BNP levels (80 ± 35 pg ml⁻¹). The regression analysis of the initial parameters found RVDI to be the strongest predictor (R² = 0.61; P<0.0001) for BNP level, whereas RVDI reduction was the strongest factor for BNP decrease (R² = 0.65; P<0.0001) during FUV.. Right ventricle should be taken into account as a potential important source of plasma BNP owing to the fact that LV size and function are well preserved in MVS patients. RVDI determines BNP plasma levels whereas after MVS removal, the RVDI reduction predicts BNP level decrease.

Topics: Aged; Biomarkers; Case-Control Studies; Down-Regulation; Female; Heart Failure; Heart Valve Prosthesis Implantation; Heart Ventricles; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Mitral Valve Stenosis; Natriuretic Peptide, Brain; Poland; Regression Analysis; Rheumatic Heart Disease; Risk Assessment; Risk Factors; Severity of Illness Index; Time Factors; Treatment Outcome; Ultrasonography; Ventricular Function, Left; Ventricular Function, Right

Topics: Biomarkers; CA-19-9 Antigen; Chronic Disease; Female; Heart Failure; Humans; Hypertrophy, Right Ventricular; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Embolism; Ultrasonography

Troponin I (cTnI), myoglobin, heart-type fatty acid binding protein (H-FABP), and natriuretic peptides (BNP, NTproBNP) were all reported to be elevated in patients with pulmonary embolism (PE).. To assess the correlation between the aforementioned markers and helical computed tomography (hCT) right ventricular dysfunction (RVD) in non massive PE, we performed this prospective pilot study on 50 patients.. Patients with RVD had significant higher natriuretic peptides prevalence than cardiomyocytes damage-related markers (48% vs 20%, P=0.006). Significant prevalence differences were observed only for natriuretic peptides when patients with RVD and those without were compared (74% vs 33% for NT-pro BNP, P=0.005 and 65% vs 22% for BNP, P=0.003). Patients with RVD had significant higher biomarkers median plasmatic values than those without (BNP: 170 vs 36 pg/ml, P=0.0027; NT-proBNP: 1369 vs 170.7 pg/ml, P=0.0024; cTnI: 0.032 vs 0 ng/ml, P=0.0034; H-FABP: 4.32 vs 2.23 ng/ml, P=0.0032; myoglobin: 36.7 vs 28.2 ng/ml, P=0.03). Significant correlations were only obtained between RV/LV index and plasmatic natriuretic peptides (NT-proBNP: r=0.36, P=0.009; BNP r=0.28; P=0.047).. Natriuretic peptides prevalence elevation and median values are significantly higher when RVD is present and significantly correlate with hCT RVD.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Myoglobin; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Embolism; Radiography, Thoracic; ROC Curve; Tomography, Spiral Computed; Troponin I

Right ventricular systolic dysfunction (RVSD) at baseline (pre-treatment) predicts early death in patients with pulmonary hypertension (PH). However, RVSD can only be detected reliably by prohibitively invasive or expensive techniques. N-terminal B-type natriuretic peptide concentration ([NT-proBNP]) correlates with RV function in PH; however, an [NT-proBNP] threshold that indicates RVSD in individual patients has not previously been determined. Twenty-five patients with PH (pulmonary arterial hypertension (n = 19) or chronic thromboembolic PH (n = 6)) underwent cardiovascular magnetic resonance (CMR) imaging and NT-proBNP measurement at baseline. [NT-proBNP] was correlated against RV dimensions and ejection fraction (RVEF) measured directly by CMR imaging. The ability of NT-proBNP to detect RVSD (defined as a CMR-derived RVEF >2 SDS below control values) was tested and predictors of [NT-proBNP] identified. [NT-proBNP] correlated negatively with RVEF. RVSD was present in nine out of 25 patients. An [NT-proBNP] threshold of 1,685 pg.mL(-1) was sensitive (100%) and specific (94%) in detecting RVSD. RVEF and RV mass index independently predicted [NT-proBNP]. In pulmonary hypertension, a baseline N-terminal B-type natriuretic peptide concentration of >1,685 ng.L(-1) suggests right ventricular systolic dysfunction, and thus an increased risk of early death. N-terminal B-type natriuretic peptide could prove useful as an objective, noninvasive means of identifying patients with pulmonary hypertension who have right ventricular systolic dysfunction at presentation.

Topics: Aged; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Artery; Ventricular Function, Right

Topics: Animals; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Artery; Ventricular Function, Right

The authors describe a case of 21-years old woman with idiopathic pulmonary arterial hypertension with atypical clinical consequences of massive internal bleeding. Despite significant hypovolemia clinical and laboratory presentation was one of RV failure with dilatation of right heart ventricle and increased plasma level of markers of myocardial stretch and injury (NT-proBNP and troponin, respectively). This is attributed to impaired right ventricular coronary perfusion and hypoxia. Intensive treatment restored baseline RV conditions and at 15 months follow-up no persistent right heart impairment was observed. This case demonstrates that bleeding should be also considered in differential diagnosis of exacerbation of right ventricular failure in patients with pulmonary arterial hypertension.

Topics: Adult; Biomarkers; Female; Heart Failure; Hemoperitoneum; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T; Ventricular Dysfunction, Right

Cardiac volumetry by magnetic resonance imaging can guide the timing for reoperation in minimally symptomatic or asymptomatic patients with pulmonary insufficiency after corrected tetralogy of Fallot. Pro-brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and wall stress, and levels may complement magnetic resonance imaging in cardiac assessment before and after pulmonary valve replacement.. Between May 2004 and October 2005, 23 consecutive patients with corrected tetralogy, severe pulmonary insufficiency, and right ventricular end-diastolic volume index greater than 150 mL/m2 underwent elective pulmonary valve replacement. Plasma proBNP levels and magnetic resonance imaging were obtained before and 6 months after pulmonary valve replacement.. There was no surgical mortality or morbidity. Preoperative right ventricular end-diastolic volume index correlated with pulmonary insufficiency, and inversely so with left ventricular ejection fraction, reflecting interventricular interaction. Preoperatively (r = -0.47) and 6 months postoperatively (r = -0.54), log BNP was inversely correlated with right ventricular ejection fraction. Mean preoperative proBNP levels, right ventricular end-diastolic volume index, and pulmonary insufficiency significantly (p < 0.0001) diminished 6 months after pulmonary valve replacement (231 versus 114 ng/L, 184 versus 109 mL/m2, and 44% versus 2%, respectively).. Plasma proBNP is elevated in patients with corrected tetralogy, severe pulmonary insufficiency, and right ventricular dilatation, and it significantly diminishes 6 months after pulmonary valve replacement, mirroring magnetic resonance imaging-documented better right ventricular ejection fraction and smaller right ventricular end-diastolic volume index. Pro-brain natriuretic peptide complements magnetic resonance imaging for cardiac assessment in patients requiring pulmonary valve insertion. Future validation of cutoff levels are required to establish proBNP as a useful diagnostic and follow-up tool in patients with chronic pulmonary insufficiency and failing right ventricles.

Topics: Biomarkers; Child, Preschool; Disease Progression; Heart Valve Prosthesis Implantation; Humans; Hypertrophy, Right Ventricular; Infant; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Prospective Studies; Pulmonary Valve Insufficiency; Reoperation; Stroke Volume; Tetralogy of Fallot; Time Factors

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiac Catheterization; Female; Humans; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Ventricular Dysfunction, Right

We established a rat chronic alveolar hypoxia in vivo model to evaluate the efficacy against hypoxic pulmonary hypertension of a new angiotensin II-receptor I blocker, olmesartan medoxomil. Three groups of rats were established: rats exposed for 2-6 weeks to 10% oxygen atmosphere in a normobaric chamber; hypoxic rats treated with olmesartan medoxomil oral administration (5 mg/day) every day; and control rats fed in a normoxic condition. After hypoxia treatment, the presence, etiology and severity of pulmonary hypertension, was echocardiographically evaluated, and expressions of brain natriuretic peptide (BNP), transforming growth factor (TGF-beta) and endothelin-1 genes measured by both immunohistochemical assay and real-time polymerase chain reaction. Olmesartan medoxomil significantly reduced the induction of hypoxic cor pulmonale not only on echocardiographical observations but also in BNP, TGF-beta and endothelin gene expressions in molecular studies. However, systolic blood pressure was independent of olmesartan medoxomil. The present study clearly indicates that the angiotensin II-type I-receptor blocker olmesartan medoxomil has significant efficacy for hypoxic cor pulmonale.

Topics: Administration, Oral; Angiotensin II Type 1 Receptor Blockers; Animals; Antihypertensive Agents; Collagen; Disease Models, Animal; Echocardiography; Endothelins; Heart; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Imidazoles; Lung; Male; Myocardium; Natriuretic Peptide, Brain; Olmesartan Medoxomil; Pulmonary Artery; Pulmonary Heart Disease; Rats; Rats, Wistar; RNA, Messenger; Tetrazoles; Transforming Growth Factor beta

Natriuretic peptide (NP) receptors (NPRs) located at the endocardial endothelium are suggested to be involved in regulating myocardial contractility. However, the characteristics and modulation of NPRs in relation to cardiac failure are not well defined. This study examined the properties of NPRs in ventricular endocardium using quantitative receptor autoradiography, RT-PCR, Southern blot analysis, and activation of particulate guanylyl cyclase (GC) by NPs. In control rats, specific 125I-labeled rat atrial NP (rANP)(1-28) binding sites were localized in right (RV) and left ventricular (LV) endocardium. Binding affinities of 125I-rANP(1-28) were remarkably higher in RV than LV endocardium. Radioligand binding at these sites was mostly inhibited by des[Gln18,Ser19,Gly20,Leu21, Gly22]ANP(4-23), a specific NP clearance receptor ligand. mRNAs for all three recognized NPRs were detected in endocardial cells by RT-PCR and confirmed by Southern blot analysis. Production of cGMP by particulate GC in endocardial cell membranes was stimulated by NPs with a rank order of potency of C-type NP(1-22) >> brain NP (BNP)(1-26) > ANP(1-28). We also examined the modulation of these NPRs during cardiac hypertrophy induced by monocrotaline (MCT). In MCT-treated rats with pulmonary hypertension, specific (125)I-rANP(1-28) binding to hypertrophied RV endocardium almost disappeared and cGMP production by NPs was significantly decreased. In rats with pulmonary hypertension, plasma levels of ANP and BNP were increased by fivefold compared with controls. The results indicate that there is a differential distribution of NPRs in the cardiac chambers, with the most abundant binding sites in RV endocardium, that NPR-B is the predominant GC-coupled NPR in ventricular endocardium, and that endocardial NPRs are downregulated with ventricular hypertrophy. Downregulation of NPRs may be associated with an increment of endogenous NP production caused by mechanical overload in hypertrophied ventricle.

Topics: Animals; Atrial Natriuretic Factor; Autoradiography; Binding, Competitive; Cell Membrane; Cyclic GMP; Endocardium; Endothelium, Vascular; Gene Expression Regulation; Hypertrophy, Right Ventricular; Iodine Radioisotopes; Male; Myocardium; Natriuretic Peptide, Brain; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Reverse Transcriptase Polymerase Chain Reaction; Transcription, Genetic

Brain natriuretic peptide (BNP) is a pulmonary vasodilator that is elevated in the right heart and plasma of hypoxia-adapted rats. To test the hypothesis that BNP protects against hypoxic pulmonary hypertension, we measured right ventricular systolic pressure (RVSP), right ventricle (RV) weight-to-body weight (BW) ratio (RV/BW), and percent muscularization of peripheral pulmonary vessels (%MPPV) in rats given an intravenous infusion of BNP, atrial natriuretic peptide (ANP), or saline alone after 2 wk of normoxia or hypobaric hypoxia (0.5 atm). Hypoxia-adapted rats had higher hematocrits, RVSP, RV/BW, and %MPPV than did normoxic controls. Under normoxic conditions, BNP infusion (0.2 and 1.4 micro g/h) increased plasma BNP but had no effect on RVSP, RV/BW, or %MPPV. Under hypoxic conditions, low-rate BNP infusion (0.2 micro g/h) had no effect on plasma BNP or on severity of pulmonary hypertension. However, high-rate BNP infusion (1.4 micro g/h) increased plasma BNP (69 +/- 8 vs. 35 +/- 4 pg/ml, P < 0.05), lowered RV/BW (0.87 +/- 0.05 vs. 1.02 +/- 0.04, P < 0.05), and decreased %MPPV (60 vs. 74%, P < 0.05). There was also a trend toward lower RVSP (55 +/- 3 vs. 64 +/- 2, P = not significant). Infusion of ANP at 1.4 micro g/h increased plasma ANP in hypoxic rats (759 +/- 153 vs. 393 +/- 54 pg/ml, P < 0.05) but had no effect on RVSP, RV/BW, or %MPPV. We conclude that BNP may regulate pulmonary vascular responses to hypoxia and, at the doses used in this study, is more effective than ANP at blunting pulmonary hypertension during the first 2 wk of hypoxia.

Topics: Animals; Antihypertensive Agents; Atrial Natriuretic Factor; Blood Pressure; Body Weight; Heart Ventricles; Hemodynamics; Histocytochemistry; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Lung; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Sprague-Dawley; Vasodilator Agents

Adaptation of cardiac muscle to prolonged hypobaric hypoxia (770-740 mbar, 2,250-2,550 m), endurance training, and their combination was studied in rats by investigating the gene expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in atria and ventricles. Rats were assigned into the following groups according to the barometric conditions and physical activity; normobaric sedentary (NS), normobaric training, hypobaric sedentary (HS), and hypobaric training (HT). Experimental periods were 10, 21, and 56 days; the groups at 91 days served as recovery groups from exposure to and training in normobaric and hypobaric conditions for 56 days. The right ventricular hypertrophy in HT rats at 10 days and 56 days was associated with elevated BNP mRNA levels (2.1- and 1.7-fold, P < 0.05, respectively), whereas hypobaric exposure without training was not sufficient to significantly increase ventricular BNP gene expression, although it lead to hypertrophy of the right ventricle. Right and left atrial BNP mRNA levels were also increased (up to 3.9-fold, P < 0.01) in 10-day HS and 10-day HT groups. ANP mRNA levels in right ventricle and left ventricular epicardium were over twofold higher (P < 0.05-0.01) in 10-day HS and 10-day HT groups in comparison to 10-day NS group. Plasma immunoreactive ANP concentration was increased (P < 0.05) in both hypobaric groups up to 21 days. The results show that exposure to hypobaric hypoxia itself and endurance training in hypobaric, hypoxic conditions lead to a marked early increase in ventricular and atrial ANP and BNP mRNA levels. The adaptational response to hypoxia was more pronounced when the oxygen availability was lowered additionally by endurance training carried out in hypobaric hypoxic conditions.

Topics: Acclimatization; Animals; Atmospheric Pressure; Atrial Natriuretic Factor; Body Weight; Heart; Heart Atria; Hypertrophy, Right Ventricular; Hypoxia; Male; Myocardium; Natriuretic Peptide, Brain; Organ Size; Physical Conditioning, Animal; Rats; Rats, Wistar; RNA, Messenger; Time Factors; Transcription, Genetic

It has been unclear whether the increases in transcript accumulation for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) during pressure overload are caused by the direct hemodynamic stress imposed on the myocytes or mediated by systemic hormonal factors. We examined the levels and regional distributions of ANP and BNP mRNAs in the hypertrophied right ventricle produced by experimental coarctation of main pulmonary artery (PA) in rats and compared them with those of skeletal alpha-actin mRNA, which is known to be a genetic marker for cardiac hypertrophy. In this experimental model, the left ventricle was free from the influence of pressure overload. By Northern blot analysis, remarkable increases in mRNAs for ANP and BNP, as well as skeletal alpha-actin, were observed in the right ventricle at 1 day after PA banding. Changes of expression of these genes were minimal in the left ventricle. ANP mRNA levels in the right ventricle increased further at days 3 and 7, whereas BNP mRNA remained at its day 1 level through 7 days. Increased expression of ANP, BNP, and skeletal alpha-actin mRNAs occurred exclusively in the right ventricular (RV) free wall and in the junctional region between the RV free wall and the interseptal wall as determined by in situ hybridization. These data suggest that local stimuli caused by hemodynamic overload induce cardiac hypertrophy and its associated increases in ANP and BNP expression in the RV free wall.

Topics: Actins; Animals; Atrial Natriuretic Factor; Gene Expression; Heart Ventricles; Hypertrophy, Right Ventricular; In Situ Hybridization; Male; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Organ Specificity; Probability; Pulmonary Artery; Rats; Rats, Wistar; RNA, Messenger; Systole; Ventricular Pressure