Stress serves as a risk factor in the etiology of hypertension. The present study was designed to decipher the effect and mechanism of chronic stress on the progression of pressure overload-induced cardiac dysfunction. We used abdominal aortic constriction (AAC) to induce pressure overload with or without chronic restraint stress to establish the animal models. Echocardiographic analysis showed pressure overload-induced cardiac dysfunction was worsened by chronic stress. Compared with the AAC rats, there is a significant increase in cardiac hypertrophy, injury, apoptosis and fibrosis of the AAC + stress rats. Furthermore, we found the secretion of norepinephrine (NE) increased after the AAC operation, while the level of NE was higher in the AAC + stress group. Cardiomyocytes and cardiac fibroblasts isolated from neonatal rats were cultured and separately treated with 1, 10, 100 μM NE. The higher concentration NE induced more cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression. These results revealed that high level of NE-induced cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression further contributes to the effect of chronic stress on acceleration of pressure overloadinduced cardiac dysfunction., W. Liu, X. Wang, Z. Mei, J. Gong, X. Gao, Y. Zhao, J. Ma, F. Xie, L. Qian., and Obsahuje bibliografii
The question was addressed whether short-term (4 hour) NO deficiency, inducing an increase in blood pressure in anaesthetized dogs, does influence proteosynthesis in the myocardium and coronary arteries. A potentially positive answer was to be followed by the study of the supporting role of ornithine decarboxylase for the polyamines pathway. NG-nitro-L-arginine-methyl ester (L-NAME) (50 mg/kg per hour) was administered i.v. to inhibit NO synthase. After the first L-NAME dose diastolic blood pressure increased from 131.8 ±2.0 to 149.4 ±3.9 mm Hg (p< 0.001) and was maintained at about this level till the end of the experiment. Systolic blood pressure only increased after the first dose (from 150.8 ±1.1 to 175.0 ±5.8 mm Hg, p<0.01), returning thereafter to the control level. Similarly, the heart rate declined only after the first dose (from 190.4±5.3 to 147.6±4.5 beats/min, p<0.01). Total RNA concentrations increased in the left cardiac ventricle (LV), the left anterior descending coronary artery (LADCA) and left circumflex coronary artery (LCCA) by 15.9 ±0.7, 29.7 ±1.3 and 17.6 ±1.0%, p<0.05, respectively. The same applied to [14C]leucine incorporation (by 86.5 ±5.0, 33.5 ±2.6, 29.3±4.1 %, p<0.05, respectively). The above parameters indicated an increase of proteosynthesis in the LV myocardium and both coronary arteries LADCA and LCCA after short-term NO deficiency. Surprisingly, the ornithine decarboxylase activity in the LV myocardium decreased significantly by 40.2± 1.6 % (p<0.01) but the changes were not significant in the coronary arteries. This unexpected finding makes the role of polyamines in increasing proteosynthesis during a pressure overload due to NO deficiency questionable.
More than 50 % of end-stage renal disease (ESRD) patients treated by chronic hemodialysis die from cardiovascular diseases, including congestive heart failure (CHF). The incidence of CHF is rising in both general and ESRD population. However, the mechanisms, which lead to the development of CHF in dialyzed patients, differ considerably. First, there are several factors leading to increase of the left ventricular afterload: volume overload between dialyses, hypertension, increased arterial stiffness, anemia, vascular access flow (arteriovenous fistula) and sympathetic activation. Second, hypertension, left ventricular hypertrophy, anemia and frequently present coronary artery disease worsen myocardial oxygenation. The combination of these factors explains the high incidence of CHF in dialyzed patients and their roles are reviewed in this article., J. Malík ... [et al.]., and Obsahuje seznam literatury
Normal increase in hemodynamic load during early postnatal life is associated with heart growth and maturation of membrane structures that is accompanied by remodeling of membrane protein and lipid components. This review describes remodeling of phospholipids (PL) in rat myocardium during normal postnatal development and during accelerated cardiac growth induced by additional workload (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart early after birth. Normal physiological load after birth stimulates the development of membrane structures and synthesis of PL. While hyperthyroidism accelerates these processes, pressure overload has an inhibitory effect. These changes primarily influence the maturation of mitochondrial membranes as cardiolipin is one of the most affected PL species. The most sensitive part of PL structure in their remodeling process are PL acyl chains, particularly polyunsaturated fatty acids that are the key components determining the basic physicochemical properties of the membrane bilayer and thus the function of membrane-bound proteins and membrane-derived signaling lipid molecules. It is evident that PL remodeling may significantly influence both normal and pathological postnatal development of myocardium., F. Novák ... [et al.]., and Obsahuje seznam literatury
A pressure overload was induced in 2-day-old male rats by abdominal aortic constriction, and the phospholipid composition of the left ventricle (LV) and the right ventricle (RV) were determined. Sixty days after the surgery, body weights was lower and LV weight were higher in aorta-constricted (AC) rats in comparison with sham- operated animals. Increased ventricular/body weight ratios indicated a significant degree of hypertrophy of LV and smaller hypertrophy of RV. The concentrations of total phospholipids (PL), choline phosphoglycerides (PC), ethanolamine phosphoglycerides (PE), diphosphatidylglycerol (DPG) and phosphatidylinositol (PI) were decreased in both ventricles of AC rats. The concentrations of sphingomyelin (SM) and plasmalogen PE (PLPE) increased in LV only. The changes in phospholipid composition in the developing pressure-overloaded myocardium may contribute to altered membrane functions connected with heart hypertrophy.
Increasing hemodynamic load during early postnatal development leads to rapid growth of the left ventricular (LV) myocardium, which is associated with membrane phospholipid (PL) remodeling characterized by n-3 polyunsaturated fatty acids (PUFA) accumulation. The aim of this study was to examine the influence of additional workload imposed early after birth when ventricular myocytes are still able to proliferate. Male Wistar rats were subjected to abdominal aortic constriction (AC) at postnatal day 2. Concentrations of PL and their fatty acid (FA) profiles in the LV were analyzed in AC, sham-operated (SO) and intact animals on postnatal days 2 (intact only), 5 and 10. AC resulted in LV enlargement by 22 % and 67 % at days 5 and 10, respectively, compared with age-matched SO littermates. Concentrations of phosphatidylcholine, cardiolipin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine and sphingomyelin decreased in AC myocardium, albeit with different time course and extent. The main effect of AC on FA remodeling consisted in the accumulation of n-3 PUFA in PL. The most striking effect of AC on FA composition was observed in phosphatidylinositol and cardiolipin. We conclude that excess workload imposed by AC inhibited the normal postnatal increase of PL concentration while further potentiating the accumulation of n-3 PUFA as an adaptive response of the developing myocardium to accelerated growth., F. Novák, ... [et al.]., and Obsahuje seznam literatury
Aortic banding induced in 2-day-old (A2) and 6-day-old (A6) male rats increased the left ventricular (LV) weight after 60 days; right ventricular (RV) enlargement occurred in the A2 group only. The concentration of collagenous proteins in the LV was elevated in both experimental groups (more in the A2 rats) at the expenses of sarcoplasmic proteins. Aortic banding also affected the proportion of collagen types (lower collagen I, higher collagen 111, V) and myosin light chains (higher LC1/LC2) in the LV. Similar changes of proteins in the RV were less pronounced.
It is known that hypertension is accompanied by increased [Na+]i. The functional properties of Na,K-ATPase, which transports the Na+ out and K+ into myocardial cells during the relaxation phase, were investigated in the left ventricle (LV), septum (SV) and the right ventricle (RV) of anesthetized dogs with moderate acute blood pressure elevation elicited by short-term (4-hour) NO synthase inhibition. The NO-insufficiency was induced by administration of an L-arginine analogue, the NG-nitro-L-arginine methyl ester (L-NAME). Concerning the function of Na,K-ATPase under the conditions of lowered NO synthesis, we focused our attention to the binding of Na+ to the enzyme molecule. Activation of the enzyme by increasing Na+ concentrations revealed significant changes in both the maximal velocity (Vmax) and the affinity for Na+ (KNa) in all investigated heart sections. The Vmax increased by 27 % in LV, by 87 % in SV and by 58 % in RV. The KNa value increased by 86 % in LV, by 105 % in SV and by 93% in RV, indicating an apparent decrease in the sensitivity of the Na+-binding site in the Na,K-ATPase molecule. This apparently decreased pump affinity for Na+ together with the increase of Vmax suggest that, during the short-term inhibition of NO synthesis, the Na,K-ATPase is capable of extruding the excessive Na+ from the myocardial cells more effectively at higher [Na+]i as compared to the Na,K-ATPase of control animals., N. Vrbjar, M. Strnisková, O. Pecháňová, M. Gerová., and Obsahuje bibliografii
Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms α, δ and ε in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of 32P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (105 × g) and nuclear-cytoskeletalmyofilament- enriched (103 × g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the 3rd day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCδ, which increased significantly at d10 in the cytosolic fraction at the expense of the membraneenriched fraction. It is concluded that PKCα, PKCδ and PKCε undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period., B. Hamplová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy