Ventricular myosin pattern of spontaneously hypertensive turkeys is unaffected by labetalol treatment

Summary In most animal species, left ventricular hypertrophy due to pressure overload is associated with an advantageous increase of the slow V₃ isomyosin. In contrast, in spontaneously hypertensive turkeys, the development of left ventricular hypertrophy is associated with the synthesis of a fast V₁-like isomyosin, with high incidence of cardiac failure. This could be related to the high catecholamine levels found in these animals. This is why we studied the ventricular myosin pattern after lowering of blood pressure and regression of cardiac hypertrophy obtained by means of labetalol, an - and -blocking drug which inhibits the effects of catecholamines.From the 2nd to the 32nd week of age, 22 turkeys were treated with increasing doses of p.o. labetalol (from 20 to 35 mg/kg body weight daily) and 16 other turkeys were given daily p.o. placebo. Blood pressure and heart rate were periodically measured by an indirect method. After sacrifice, the degree of cardiac hypertrophy was evaluated by the biventricular weight to body weight ratio, ventricular myosin was purified, Ca⁺⁺-activated ATPase activity assessed, and ventricular myosin pattern was determined by two-dimensional gel electrophoresis of myosin heavy chains. Plasma and cardiac catecholamines were measured by high performance liquid chromatography.Throughout the study period, blood pressure and heart rate were significantly reduced in the labetalol-treated animals as compared to the untreated ones. At the end of the study period, the ventricular mass was significantly lower in the labetalol group. Nevertheless, no differences were obscrved in ventricular myosin pattern and Ca⁺⁺-activated ATPase activity levels between the two groups. In the labetalol group, an increase in plasma catecholamines and only a slight, but not significant, increase in cardiac catecholamines was found.These data indicate that in spontancously hypertensive turkeys, the synthesis of the fast V₁-like isomyosin is not influenced by known pathophysiological stimuli like blood pressure, cardiac hypertrophy and catecholamines.     

Increased calcium sensitivity of chemically skinned human atria by myosin light chain kinase

Summary We investigated the influence of myosin P-LC phosphorylation catalysed by calcium/calmodulin-dependent myosin light chain kinase (MLCK) on the tension-pCa relation of chemically skinned human atrial fibres. MLCK-induced increased myosin P-LC phosphorylation sensitized human atrial skinned fibres for calcium by 0.11 pCa-units in patients with valvular heart disease, and by 0.05 to 0.07 pCa-units in patients with coronary heart disease. The MLCK effect could be antagonized by a light chain phosphatase. The protein phosphatase ocadaic acid (OA) had no influence on the tension-pCa relation of skinned human atrial fibres and had no potentiating effect together with MLCK. The MLCK preparation used in this study was from bovine ventricle and revealed a K_M of 1.8×10^–5 M and a V_max of 822 nmol P_i/min/mg using purified bovine ventricular myosin-LCs as substrate.     

Causative role of coronary microvessels for the development and progression of chronic myocardial lesions in spontaneously hypertensive rats (SHR)

Summary The pathomechanisms responsible for the development and progression of myocardial alterations in hypertensive heart disease are largely unknown. Using newly developed preparation and measuring procedures in 78 SHR and 82 controls aged 3–78 weeks, topological relations were detected between focal morphological appearances of chronic myocardial ischemia (fml.) and pathological microvessel (mv.) reactions characterized by morphometric signs of chronic contractions. The smallest ramifications are of particular pathogenic importance. A generalized peak of pathological mv. reactions between the 16th and 24th weeks is responsible for the development of first fml. The further progression of the area density of fml. from 1.26±0.85% (24th week) to 31.82±8.60% (78th week) is attributable to the further increase in pathological mv. reactions caused by organ-specific influences. The histological and morphometric findings suggest that the pathological mv. reactions are aggrevated by their own effects at the local level.Abbreviations d diameter - fml focal myocardial lesions - mv microvessel(s) - SDH succinodehydrogenase     

Cardiac sarcoplasmic reticulum characteristics in hypertrophic hearts from spontaneously hypertensive rats

Summary Sarcoplasmic reticulum (SR) from left ventricles of rats that developed spontaneous hypertension was studied in vitro. Similar increases of left ventricular mass were found when grouping the animals into mild and severe hypertensives (average systolic arterial pressure of 168±4 and 202±6 mm Hg, respectively). The amount of SR protein (mg/g of left ventricle) was higher when obtained from hypertrophic ventricles of both hypertensive groups than from ventricles of the control group. The result agreed with the enhanced Ca²⁺ uptake exhibited by left ventricular homogenates of the hypertensive groups. Consequently, Ca²⁺ uptake in SR microsomes isolated per gram of left ventricle (nmol Ca²⁺/g muscle) was 51.62±10.06 and 64.99±12.84 in mildly and severely hypertensive groups vs. 17.37±5.79 in the control group (P<0.05). The SR microsomes obtained from ventricles of hypertensive rats showed an enhanced Ca²⁺ activated ATPase activity that was not accompanied by increased Ca²⁺ uptake at saturating calcium concentrations, but by increased affinity for calcium (K'_app of 1.09±0.28 and 2.67±0.16 M in SR microsomes of hypertrophic and control ventricles respectively; P<0.05). The rats of calcium loss, measured in SR vesicles passively loaded with⁴⁵Ca, were similar when assayed in SR obtained from ventricles of both hypertensive and normal rats. These results enable us to suggest that in hearts of rats presenting spontaneous hypertension, the function of the SR system could account for a normal handling of cytosolic calcium. They might support the absence of mechanical alterations described in hearts of young rats of the SHR strain.This work was supported by grants from the Consejo nacional de Investigaciones Científicas y Tecnicas de la República Argentina (CONICET).     

Effects of caffeine on energy output of rabbit heart muscle

Summary The effects of caffeine (1 mmol·1^–1) on mechanical and energetic parameters in the arterially perfused interventricular rabbit septa were examined at various frequencies of stimulation. Even though 1 mmol^–1 caffeine induced a negative inotropic effect only at stimulation rates higher than 0.33 Hz. relaxation was impaired at all frequencies tested. The ratio between maximum rate of relaxation and developed tension was consistently lowered by caffeine, indicating a more marked effect on relaxation over contraction. In addition, while time-to-peak tension was unaffected by caffeine at the dose used, the last part of the relaxation (i.e., of the contractile event) was prolonged at all frequencies in the presence of the drug. Resting heat production (H _t ) was increased in the presence of caffeine (1.6±0.6 mW·g^–1). The ratios between active heat production and either developed tension (H_a/T) or tension time integral (H_a/TtI), increased at all frequencies examined (53.3±8.5 J·mN^–1·g^–1 and 68.2±9.9 J·mN^–1·s^–1·g^–1, respectively), indicating a lowered economy of the contractile process. This is consistent with the lower ATP/Ca ratio reported for the sarcoreticular Ca pump (i.e., one ATP hydrolyzed/2 Ca transported) with respect to the sarcolemmal mechanisms such as Na–Ca exchanger or the sarcolemmal Ca pump, with an ATP/Ca ratio of 1 to 1. Thus, inhibition of the SR-Ca pump by caffeine would induce a higher rate of ATP hydrolysis with the consequent increase in the H_a/T ratio. As a result of the increase in both H_a/T ratio and H_r induced by caffeine, the ratio between total heat production and developed tension (H_t/T) also increased. Therefore, the contractile process appeared to be more efficient in the presence of an active SR, since it is energetically less costly to generate a given level of isometric tension.     

Myosin P-light chain isoenzymes in the human heart: evidence for diphosphorylation of the atrial P-LC form

Summary We studied myosin light chains (LC) of human atrium and ventricle of normal and diseased individuals by a high-resolution 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE) technique. Atrial LCs (ALC-1, ALC-2 (=P-LC)) revealed both higher molecular weights and lower isoelectric points (IEP) than their ventricular counterparts (VLC-1, VLC-2 (=P-LC)). Different P-LC forms with their distinct myosin isoenzymes have been designated as P-LC-polymorphism and myosin P-LC isoenzymes, respectively. In the dephosphorylated state two VLC-2 forms (VLC-2 and VLC-2*) with the same MW and different IEP, but only one ALC-2 form, were found. In the partially phosphorylated state ALC-2 appeared to be single- and double-phosphorylated (three spots in the 2D-PAGE), whereas the two VLC-2 forms appeared to be single-phosphorylated each (four spots in the 2D-PAGE). Phosphoryl-transfer from ATP to the P-LC forms was studied using skinned fibers incubated with MLCK (myosin light chain kinase) and (-³²P)ATP. Ventricular myosin P-LC isoenzyme pattern was usually the same in normal and diseased patients: the VLC-2 to VLC-2* ratio was approx. 70/30, but in one patient with valvular heart disease (VHD) the relation was 55/45 (shift to the VLC-2* form). In hypertrophied atria of VHD patients a shift of the myosin P-LC isoenzyme pattern to the VLC-2* form occurred, too.     

Effects of riboflavin analogues and diuretics on the spontaneously hypertensive rat heart

Summary The chronic treatment of spontaneously hypertensive rats (SHR) with 7,8-dimethyl-10-(3-chlorobenzyl) isoalloxazine [CBI], 7,8-diethyl-10-aminol isoalloxazine [DEAI], enduron (methyclothiazide) and amiloride were studied for their effects on blood pressure and cardiac contractile protein ATPasc activities. After 35 weeks of treatment all the above antihypertensive agents showed a decrease in blood pressure in the SHR (p<0.01). Chronic treatment with CBI, DEAI, enduron, and amiloride significantly improved the myofibrillar ATPasc activity at all pCa²⁺ concentrations (p<0.01). Furthermore, CBI, DEAI, enduron, and amiloride drug treatments enhanced actin-activated myosin ATPase activity (p<0.01). The Ca²⁺-activated myosin ATPase activity was significantly elevated after treating with CBI and DEAI (p<0.01). These results suggest that the antihypertensive agents used in this study helped in reducing the blood pressure with a subsequent increase in myocardial contractile protein ATPase activity.     

Antiproliferative effects of a c-myc antisense oligonucleotide on human arterial smooth muscle cells

Summary The effects of a c-myc antisense phosphorothioate DNA oligonucleotide were assessed on the proliferation rate of human arterial smooth muscle cells (HSMCs). Compared to a control oligonucleotide the antisense oligonucleotide suppressed the proliferation of HSMCs in a concentration-dependent manner without a major cytotoxic effect. Outgrowth of HSMCs from media explants was significantly inhibited as well. Induction of c-myc expression by serum stimulation of cells was blunted by the antisense oligonucleotide, as shown by immunoblotting.These results demonstrate that c-myc expression is an essential factor for proliferation of HSMCs after growth stimulation, and they show the potential of antisense technology for modulating gene expression of HSMCs in vitro.Supported by a grant fromt the SFB 330Results of the study have been presented at the XIIIth Congress of the European Society of Cardiology (1991) and the 64th Scientific Session of the American Heart Association (1991)     

Effects of triiodothyronine in spontaneously hypertensive rats. Studies on cardiac metabolism,function, and heart weight

Summary We have studied the effects of triiodothyronine (T₃) on heart function,on the myocardial oxidative pentose phosphate pathway, and on heart weight in spontaneously hypertensive (SHR) rats. Another aim was to examine whether these T₃-effects may be reversible. T₃ was administered daily (0.2 mg/kg s. c.) for 14 days. Compared to the untreated SHR controls, T₃ induced an increase in heart rate (beast/min) from 357±10 (n=17) to 553±10 (n=17), in the pressure-rate-product (mm Hg/min) from 78400±4500 (n=15) to 113700±4800 (n=15), and in the heart weight/body weight ratio (mg/g) from 4.2±0.2 (n=20) to 5.8±0.2 (n=19). The activity of myocardial glucose-6-phosphate dehydrogenase, the first and rate-limiting enzyme of the oxidative pentose phosphate pathway (units/g protein), was clevated from 4.2±0.2 (n=9) to 7.0±0.6 (n=9) after 14 days of T₃-treatment while the activity of 6-phosphogluconate dehydrogenase, one of the following enzymes in the pathway, was not altered appreciably. These changes returned to the respective control values when T₃-treatment was discontinued for 14 days. Our results demonstrate that T₃ had a positive chronotropic effect and induced an additional heart enlargement in an animal model with already established cardiac hyperfunction and hypertrophy. The effects on heart function and weight, which were fully reversible, were not as pronounced as in normal Sprague-Dawley rats.     

Effect of sarcomere length and filament lattice spacing on force development in skinned cardiac and skeletal muscle preparations from the rabbit

Summary Skinned cardiac and skeletal muscle freeze-dried preparations were activated in solutions strongly buffered for Ca²⁺. The response of single skeletal muscle fibres or thin strips of papillary muscle was investigated in relation to changes in Ca content of the perfusate. Sarcomere length was set and controlled during the experiments. The relation between the negative logarithm of the Ca concentration, the pCa, and the normalized developed force proved to be sigmoidal. The exact position of these curves proved to be dependent upon both sarcomere length and the distance between the filaments. The latter was shown by means of osmotic compression of the fibres using dextran. As a consequence of these observations. it was concluded that the length-tension relation is dependent upon the actual Ca concentration. The results are discussed in terms of cross-bridge interaction.     

1,2-Diacylglycerol content in myocardium from spontaneously hypertensive rats during the development of hypertension

Summary 1,2-Diacylglycerol (DAG) has been considered to play an important role as an activator of protein kinase C in the signal transduction of inositol phospholipid metabolism. To examine the relation of 1,2-DAG in heart tissues to cardiac hypertrophy associated with hypertension, we measured the amount of 1,2-DAG in spontaneously hypertensive rat (SHR) hearts at 4,10 and 20 weeks of age, and in age-matched normotensive Wistar-Kyoto (WKY) rat hearts using thin-layer chromatography with flame ionization detection (TLC-FID). Significant cardiac hypertrophy was found in 4-week-old SHR, while SHR did not yet have significant hypertension. Major phospholipids such as phosphatidylcholine and phosphatidylethanolamine increased from 4 to 20 weeks in the myocardium, but there was no difference between the two strains. The cholesterol levels of 4- and 20-week-old SHR were significantly higher than WKY rats. The 1,2-DAG contents of SHR hearts were significantly higher than WKY rats at 4 weeks. An increase in the RNA contents of SHR hearts were significantly higher than WKY rats at 4 weeks. An increase in the RNA content was also observed in 4-week-old SHR hearts. However, analysis of the fatty acid composition of 1,2-DAG revealed no difference between the two strains. However, there was no significant difference in the 1,2-DAG content or in its fatty acid composition between SHR and WKY rat hearts at 10 and 20 weeks of age. It is suggested that an increase in the 1,2-DAG content of SHR hearts during the early stages appears related to the initiation of cardiac hypertrophy in SHR hearts before developed hypertension.     

Atrial and ventricular myosins from human hearts. I. Isoenzyme distribution during development and in the adult

Summary Two distinct types of native isomyosins, referred to as human fetal HF and human ventricular myosin HV-3, have been identified in the human fetal heart during two different periods of gestation and in the neonatal state, whose relative parts change with development. In the adult ventricle, only HV-3 was found. Two myosin isoforms designated as HA-3 and HA-1 occur in the atrial myocardium of the normal human heart, which are electrophoretically distinct from the fetal isoenzymes.In fetal tissue, the myosin light chain complement is composed of atrial and ventricular light chains. In support of recent results, we also found identical spots from the atrial ALC-1 and the fetal light chain FLC, suggesting a homology between them. Apart from the light chains typical for this tissue, the atrial myocardium also contains ventricular light chains. Therefore we hypothesize that atrial myosin consists of two atrial isoenzymes and presumably of a ventricular type, too.Differences between atrial and ventricular myosin from human hearts were demonstrated by measuring the temperature dependence of the Ca²⁺-ATPase.     

Changes in myosin and creatine kinase mRNA levels with cardiac hypertrophy and hypothyroidism

Summary Rats were treated with three methods which produce alterations in the expression of myosin isozymes: coarctation of the abdominal aorta, treatment with low doses of isoproterenol, and administration of propylthiouracil. The steady-state levels of the left ventricle mRNAs for myosin heavy chain (-MHC), myosin heavy chain (-MHC), M creatine kinase (MCK), and B creatine kinase (BCK) were then determined using Northern and slot blot hybridizations. Cardiac hypertrophy was induced by an acute systolic pressure overload, or adrenergic stimulation. At 7 days following systolic pressure overload, the induced cardiac hypertrophy was accompanied by alterations in the levels of MHC mRNAs, as has been previously reported. In RNA from left ventricles of treated animals -MHC mRNA levels decreased by 15% by day 3 and 20% by day 7. In contrast, -MHC mRNA levels increased to 250% of control levels by day 3 and then declined to a value 150% of controls by day 7. Levels of MCK and BCK mRNAs showed little or no changes by day 3; at day 7 both MCK and BCK mRNAs showed decreases of 20% relative to controls. Cardiac hypertrophy induced by low doses of isoproterenol produced decreases of -MHC mRNA levels to 70% of control values at day 3 and 50% at day 7. Over the same time periods there was an increase in the levels of the fetal mRNA isoform (-MHC) to 190%, then 130% of control values, respectively. At 3 days, both BCK and MCK mRNA levels had declined by approximately 20–25%. By 7 days, MCK mRNA levels had decreased by approximately 50% and BCK mRNA levels by 30%. Hypothyroidism induced by PTU treatment led to a 50% decrease in -MHC mRNA levels by day 3, which then further decreased to 10% of control levels at day 7. -MHC mRNA levels increased to 350% of control levels at day 3 and then decreased to 275% of control levels at day 7. For creatine kinase mRNAs the level of the M isoform was increased by 30% at day 3, whereas there appeared to be no significant change in levels of B isoform mRNA at this time. At day 7 neither BCK nor MCK mRNA levels were significantly different from controls. These results show three treatments which produce an alteration in myosin mRNA isoforms produce little or no change in creatine kinase isoform mRNAs. Thus, the MHC and CK genes respond differently to either cardiac hypertrophy or a reduction in thyroid hormone levels.This work was supported by grants from the American Heart Association, Kansas Affiliate and the University of Kansas Center on Aging.     

Morphological and smooth muscle cell phenotypic changes in fetal rabbit aorta during early development

Summary Previous studies from our laboratory noted a) high aortic cholesterol esterification activity in the fetal rabbit, and b) increased susceptibility of fetal aortic explants to smooth muscle cell proliferation in culture, two features commonly associated with atherogenesis. This prompted us to examine in detail morphological development of fetal aorta and its relationship to fetal plasma cholesterol levels. Our studies made three important observations: 1) plasma cholesterol levels were high in early fetus which decreased at term; 2) in early fetus aortic endothelial cells appear to protrude into the lumen, whereas at birth the cells become flat, forming a continuous endothelium sheet; 3) in early fetus, smooth muscle cells exist predominantly in synthetic phenotype, while at birth the cells appear contractile. Despite the presence of synthetic smooth muscle cells and hypercholesterolemia in early fetal life, no accumulation of lipids was evident under transmission electron microscopy.     

Atrial and ventricular myosins from human hearts II. Isoenzyme distribution after myocardial infarction

Summary Human atrial and ventricular myosins were prepared from autopsy specimens from subjects with coronary heart disease. Cardiac myosin light chain isotypes were resolved using twodimensional gel electrophoresis, whereas myosin isozymes were detected by pyrophosphate gel electrophoresis.Myocardial infarction and associated work overload cause a transition in the light chain complements of the myosins. Thus ventricular myosin light chains were found in pressure overloaded atria and atrial light chains have also been identified in the infarct ventricle of the human heart.Two molecular isoenzymes of the human atrial myosin, the relative proportions of which are changed after infarction, were separated under non-dissociating conditions by gel electrophoresis. A decrease in HA-3 and a corresponding increase in HA-1 were observed. Ventricular hypertrophy in patients with coronary insufficiency induces a second ventricle isomyosin, called HV-1, with the same electrophoretic mobility as HA-1. The relative part of this myosin type amounts to 20%. Comparative peptide mapping studies were carried out on myosin subfragment-1 preparations from normal and infarct ventricles. In the primary structures, the chymotrypsic digestions produced slight differences.These data demonstrate the heterogeneity of human atrial and ventricular myosins in patients with coronary heart disease.     

Mechanical catecholamine responsiveness and myosin isoenzyme pattern of pressure-overloaded rat ventricular myocardium

Summary Pressure-overloaded cardiac hypertrophy was induced by abdominal aortic constriction in 10-week-old male Wistar rats. 24–26 weeks after aortic constriction, the hearts were excised and a myocardial mechanical study was performed using isolated left ventricular papillary muscles. There was no significant difference in isometric developed tension (T) between sham-operated control and aortic constriction (AC) rats (control vs AC rats=2.9±0.6 vs 2.7±0.7 g/mm²). dT/dt_max of AC rats, on the other hand, was significantly lower than that of controls (controls vs AC rats=32.8±7.5 vs 26.3±6.1 g/mm²sp<0.05). Myocardial mechanical responses to isoproterenol (10^–7 mol/l) were depressed in the group with aortic constriction compared with the control group (T:18.5±6.7 vs 12.1±4.9%,p<0.05, dT/dt: 25.2±6.2 vs 17.5±5.8%,p<0.02). Responses of the parameters to dibutyryl cyclic AMP (10^–5 mol/l) were also smaller in the AC group than in the control group (T: 18.0±5.6 vs 13.3±4.0%,p<0.05, dT/dt: 20.4±6.9 vs 14.7±4.1%,p<0.05). Left ventricular myosin isoenzyme pattern, revealed by pyrophosphate gel electrophoresis, shifted towards VM-3 under pressure overload. The present study demonstrates that post-membrane processes may be mainly responsible for the decreased myocardial mechanical catecholamine responsiveness in pressure-overloaded cardiac hypertrophy.Supported by Tanaka Memorial Medical Research Fund     

Heterogeneity of the response of venous smooth muscle to arterial endothelium-derived relaxing factor (EDRF) in respect of the role of nitric oxide

Summary In bioassay and organ bath experiments, the responses of different canine venous preparations to arterial and their own EDRF were studied. Vena jugularis, vena femoralis and vena mesenterica relaxed on both EDRFs released by acetylcholine. Vena saphena, venae cordis and vena portae did not showendothelium-dependent dilation, either under bioassay or in organ bath experiments. All the veins tested relaxed completely after sodium nitroprusside administration. The identity of EDRF and nitric oxide is not confirmed by this study.     

The idiopathic dilated cardiomyopathy in man. A biochemical and molecular study on myosin

Summary We studied subunit composition and Ca⁺⁺-activated ATPase activity of myosin isolated from atria and ventricles of hearts explanted from patients suffering from idiopathic dilated cardiomyopathy. At variance with previously published data, we have been unable to detect in the ventricular subendocardial layers a significant amount of myosin atrial-like light chain 1 (ALC1), which has been reported to be related to some hemodynamic features of the hypertrophied and failing heart. Such a subunit was not visible in the septum and in the subepicardial layers either. On the contrary, in both atria a ventricular-like light chain 2 (VLC2) was found. The nature of this additional light chain was confirmed on the basis of two-dimensional electrophoresis and immunoblotting techniques with polyclonal antibodies reacting with VLC2. In these patients we also observed a depressed Ca⁺⁺-activated ATPase activity, both in atrial and ventricular myosin. The explanation for this finding in ventricles still remains obscure since neither myosin light chains, nor myosin heavy chains showed any difference between patients with dilated cardiomyopathy and controls. On the contrary, in atria we clearly identified changes consistent with the expression of myosin heavy chains of ventricular type and VLC2, which can account for the depressed Ca⁺⁺-activated ATPase activity.     

Differential effect of nicotinic acid derivatives on smooth muscle and endothelial cell proliferation

Summary The pathogenesis of atherosclerosis is a multifactorial process. A possible anti-atherosclerotic drug should therefore interfere with different targets that are important during the development of an atherosclerotic lesion. Two of the early events are the activated migration and proliferation of arterial smooth muscle cells. Here we investigated in several in vivo and in vitro experiments the effect of two nicotinic acid derivatives L44 and L44-0, on smooth muscle cell migration and proliferation. Balloon catheter de-endothelialization was used as an animal model for intimal lesion formation. Migration was subsequently quantified in vitro using the explant outgrowth technique. Subcultured smooth muscle and endothelial cells were used to test the effect of the drugs on proliferation. Time-lapse video microscopy was applied to differentiate between smooth muscle cell migration and proliferation on the level of individual cells. We showed that L44 and L44-0 are very effective in decreasing smooth muscle cell proliferation and migration. Endothelial cell proliferation, important to re-establish endothelial integrity was, however, not affected.     

Changes in ECG,plasma and myocardial lipids in experimental myocardial hypertrophy in rats

Summary ECG, systolic blood pressure (BP), the ratio (R) of grams of myocardial mass/100 g of body mass, total lipids, cholesterol, triglycerides and phospholipids in blood plasma and the left ventricular myocardium, as well as the plasma free fatty acids, were investigated in 58 male Wistar rats 3,30 and 180 days after operation, in a model of myocardial hypertrophy (MH) induced by experimental coarctation hypertension, after the method of Sclye.An attempt was made to correlate some functional and metabolic indices which characterize the development of this type of MH. On a background of progressively rising BP and parallel increasing R, ECG change were recorded. They were typical of the respective stage of arterial hypertension and MH and expressed mostly in a shifting of the electrical axis of the heart to the left and in essential repolarization disturbances. The most significant changes in the studied lipid fractions were found 30 days after the induction of hypertension. The pathological changes manifested on the 180th day are discussed in relation to age, the stage of hypertension and especially in relation to the developing hypoxic and ischaemic myocardial damage.