Developmental changes of intracellular Ca2+ transients in beating rat hearts

Postnatal maturation of the rat heart is characterized by major changes in the mechanism of excitation-contraction (E-C) coupling. In the neonate, the t tubules and sarcoplasmic reticulum (SR) are not fully developed yet. Consequently, Ca(2+)-induced Ca(2+) release (CICR) does not play a central role in E-C coupling. In the neonate, most of the Ca(2+) that triggers contraction comes through the sarcolemma. In this work, we defined the contribution of the sarcolemmal Ca(2+) entry and the Ca(2+) released from the SR to the Ca(2+) transient during the first 3 wk of postnatal development. To this end, intracellular Ca(2+) transients were measured in whole hearts from neonate rats by using the pulsed local field fluorescence technique. To estimate the contribution of each Ca(2+) flux to the global intracellular Ca(2+) transient, different pharmacological agents were used. Ryanodine was applied to evaluate ryanodine receptor-mediated Ca(2+) release from the SR, nifedipine for dihydropyridine-sensitive L-type Ca(2+) current, Ni(2+) for the current resulting from the reverse-mode Na(+)/Ca(2+) exchange, and mibefradil for the T-type Ca(2+) current. Our results showed that the relative contribution of each Ca(2+) flux changes considerably during the first 3 wk of postnatal development. Early after birth (1-5 days), the sarcolemmal Ca(2+) flux predominates, whereas at 3 wk of age, CICR from the SR is the most important. This transition may reflect the progressive development of the t tube-SR units characteristic of mature myocytes. We have hence directly defined in the whole beating heart the developmental changes of E-C coupling previously evaluated in single (acutely isolated or cultured) cells and multicellular preparations.     

Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats

Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca(2+) cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca(2+) transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5-9 mo compared with 6 mo. Ca(2+) transient duration increased at 9 mo in SHRs, indicating changes in Ca(2+) reuptake during decompensation. Cell-to-cell variability in Ca(2+) transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca(2+) transient kinetics during disease progression. Vulnerability to intercellular concordant Ca(2+) alternans increased at 9-22 mo in SHRs and was mirrored by a slowing in Ca(2+) transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca(2+) alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca(2+) waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca(2+) cycling develop in SHRs long before symptoms of HF occur. Defective Ca(2+) cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca(2+) alternans and Ca(2+) wave activity, thus increasing the propensity for arrhythmogenesis in HF.     

Metallothioneins in spontaneously hypertensive rat liver.

The metallothionein (MT) synthesis was induced in the liver of spontaneously hypertensive rats (SHR) and Wistar Kyoto (WKY) rats through sc injections of CdCl2 for 3 and 6 days. The MT contents of the liver of these animals and of untreated rats from both groups were determined by gel filtration, HPLC, SDS/PAGE and amino acid analysis. The isoforms MT1 and MT2 were identified and their Cd, Zn and SH-group contents were determined. The SHR showed significantly higher values of MT than WKY rats in the untreated animals and on the 3rd day of the induction. On the 6th day, the MT levels in both groups were equal. The Cd and Zn contents followed the MT concentration in the homogenates. The possible relation between the arterial hypertension and the zinc and copper homeostasis is discussed.     

Age-related changes in serum proteins of the spontaneously hypertensive rat

Urinary protein excretion and composition in spontaneously hypertensive rats (SHR) change dramatically with age and sex. In this study, serum proteins were analyzed by electrophoresis in male and female SHR and Wistar-Kyoto (WKY) normotensive controls aged 5 to 80 weeks. Serum albumin concentrations of SHR were significantly higher than those of WKY at 5 (4.02 +/- 0.24 vs 3.60 +/- 0.25 g/dl) and 20 weeks (4.30 +/- 0.30 vs 3.77 +/- 0.31 g/dl) and significantly lower at 73-80 weeks (2.73 +/- 0.33 vs 3.45 +/- 0.34 g/dl). In addition, male SHR had significantly lower albumin levels than female SHR after 40 weeks of age. These differences may contribute to the development of hypertension and reflect the appearance of pathologic proteinuria in SHR. In spite of their differences in albumin concentrations, the fractional composition of serum protein from SHR and WKY were undistinguishable. All animals, regardless of strain or sex, manifested a significant decline in the relative amounts of albumin and low molecular weight protein and a significant increase in the relative amount of high molecular weight protein with increasing age. The etiology and significance of these age related changes in the fractional composition of serum protein are unknown, but they differ from the normal developmental pattern in humans.     

Early developmental changes in intracellular Ca2+ stores in rat brain.

Developmental changes in intracellular Ca2+ stores in brain was studied by examining: (1) IP3- and cADPR-induced increase in [Ca2+]i in synaptosomes; (2) Ca(2+)-ATPase activity and ATP-dependent 45Ca2+ uptake into Ca2+ store in ER microsomes; (3) TG-induced inhibition of Ca(2+)-ATPase activity and ATP-dependent 45Ca2+ uptake into Ca2+ store in ER microsomes; and (4) gene expression of Ca(2+)-ATPase pump in neurons obtained from brains of the new-born and the 3-week-old rats. IP3 (EC50 310 +/- 8 nM, 200% maximum increase in [Ca2+]i) and cADPR (EC50 25 +/- 3 nM, greater than 170% maximum increase in [Ca2+]i) both were potent agonist of Ca2+ release from internal stores in synaptosomes obtained from the 3-week-old rats. However, IP3 (EC50 250 +/- 10 nM, 175 maximum increase in [Ca2+]i) was a potent, but cADPR (EC50 300 +/- 20 nM, 75% maximum increase) was a poor agonist of Ca2+ release from intracellular stores in synaptosomes obtained from the new-born rats. [3H]IP3, [32P]cADPR and [3H]Ry binding in the new-born samples were significantly less than that in the 3-week-old samples. [3H]Ry binding to its receptor was more sensitive to cADPR in microsomes from the 3-week-old rats than those from the new-born rats. Microsomes from the new-born rats exhibited TG-sensitive (IC50 30 +/- 4 nM) and TG-insensitive forms of Ca(2+)-ATPase, while microsomes from the 3-week-old rats exhibited only the TG-sensitive form of Ca(2+)-ATPase (5 +/- 1 nM IC50). Microsomes from the 3-week-old rats were more sensitive to TG but less sensitive to IP3, while microsomes from the new-born rats were more sensitive to IP3 but less sensitive to TG. The lower TG sensitivity of the new-born Ca2+ store may be because they poorly express a 45 amino acid C-terminal tail of Ca(2+)-ATPase that contains the TG regulatory sites. This site is adequately expressed in the older brain. This suggests that: (1) the new-born brain contains fully operational IP3 pathway but poorly developed cADPR pathway, while the older brain contains both IP3 and cADPR pathways; and (2) a developmental switch occurs in the new-born Ca(2+)-ATPase as a function of maturity.     

Effects of oxidative stress on the expression of antioxidative defense enzymes in spontaneously hypertensive rat hearts

Little is known concerning the effect of oxidative stress on the expression of antioxidative enzymes in the decompensated cardiac hypertrophy of spontaneously hypertensive rats (SHR), considered as a model of dilative cardiomyopathy in man. Superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx) were characterized in isolated perfused hearts of 18 month old SHR and the age-matched normotensive control Wistar-Kyoto (WKY) rats, before and after 30 min infusion of 25 microM H(2)O(2). After infusion of H(2)O(2), aortic flow decreased in WKY from 26.2 +/- 2.2 to 16.0 +/- 0.8 ml/min (p <.05) but not in SHR (18.2 +/- 1.9 vs. 20.7 +/- 2.2 ml/min). This protection was related to the higher myocardial activities of GPx, MnSOD and CuZnSOD in SHR, compared with those of the WKY group. Although total SOD activity in the SHR fell after H(2)O(2) exposure (to 1.81 +/- 0.13 from 3.56 +/- 0.49 U/mg of protein), catalase activity increased (to 2.46 +/- 0.34 from 1.56 +/- 0.29 k min(-1)mg(-1)protein), compared with the pre-infusion period (p <.05 in each case). In additional studies, hearts were subjected to 30 min of global ischemia followed by 30 min of reperfusion. The results obtained in ischemic/reperfused hearts show the same changes in enzyme activities measured as it was observed in H(2)O(2) perfused hearts, indicating that oxidative stress is independent of the way it was induced. The higher catalase activity derived from elevated mRNA synthesis. The antioxidative system in dilative cardiomyopathic hearts of SHR is induced, probably due to episodes of oxidative stress, during the process of decompensation. This conditioning of the antioxidative potential may help overcome acute stress situations caused by reactive oxygen species in the failing myocardium.     

Time-course changes of myogenic tone of mesenteric small artery in spontaneously hypertensive rat

To investigate the time-course changes of myogenic tone in mesenteric small artery (MSA) of spontaneously hypertensive rat (SHR), thirty-two 7-week aged SHR rats were randomly divided into four groups (8, 16, 24, 32 weeks of age), and 32 sex- and age-matched Wistar-Kyoto (WKY) rats were assigned to control groups (CON). On the day of the study, segments of MSA were isolated and then cannulated to the two pipettes. Vascular diameters in response to the increased intraluminal pressure (from 0 mmHg to 150 mmHg, by 25 mmHg steps) of isolated MSA under no-flow conditions were recorded by a Pressure Myograph System both in physiologic salt solution (PSS) (active diameter, Da) and calcium-free PSS (passive diameter, Dp). The myogenic tone was calculated by (Dp - Da)/Dp × 100%. The tail artery pressure and vascular myogenic tone in SHR rats were significantly higher than those of the CON rats. Before 24 weeks, the vascular myogenic tone of MSA in SHR group increased monotonically, but at the end of 32 weeks, the vascular myogenic tone decreased in comparison with that in 24-week group, but was significantly higher than that in CON group. The tail artery pressure in SHR group slowly increased monotonically with increasing weeks of age, and the tail arterial pressure in 32-week group remained significantly higher than that in 24-week group. Vascular myogenic tone may participate in the whole process of hypertension. Early in the development of hypertension, because of the compensatory role of vascular tone, the vascular function has been partially compensated, thus guaranteeing adequate blood supply to organs. Late in the development of hypertension, because of the decompensation of myogenic tone, the vascular function is damaged, leading to the occurrence of severe vascular disease.     

Relative systolic dysfunction in female spontaneously hypertensive rat myocardium.

Hypertension and exercise independently induce left ventricular (LV) remodeling and alter LV function. The purpose of this study was to determine systolic and diastolic LV pressure-volume relationships (LV-PV) in spontaneously hypertensive rats (SHR) with and without LV hypertrophy, and to determine whether 6 mo of exercise training modified the LV-PV in SHR. Four-month-old female SHR (n = 20), were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (approximately 60% peak O2 consumption, 5 days/wk, 6 mo), while age-matched female Wistar-Kyoto rats (WKY; n = 13) served as normotensive controls. The LV-PV was determined using a Langendorff isolated heart preparation at 4 (no hypertrophy: WKY, n = 5; SHR, n = 5) and 10 mo of age (hypertrophy: WKY, n = 8; SHR-SED, n = 8; SHR-TRD, n = 7). At 4 mo, the LV-PV in SHR was similar to that observed in WKY controls. However, at 10 mo of age, a rightward shift in the LV-PV occurred in SHR. Exercise training did not alter the extent of the shift in the LV-PV relative to SHR-SED. Relative systolic function, i.e., relative systolic elastance, was approximately 50% lower in SHR than WKY at 10 mo of age (P < 0.05). Doppler-derived LV filling parameters [early wave (E), atrial wave (A), and the E/A ratio] were similar between groups. LV capacitance was increased in SHR at 10 mo (P < 0.05), whereas LV diastolic chamber stiffness was similar between groups at 10 mo. Hypertrophic remodeling at 10 mo of age in female SHR is manifest with relative systolic decompensation and normal LV diastolic function. Exercise training did not alter the LV-PV in SHR.     

Decreased intracellular free magnesium in erythrocytes of spontaneously hypertensive rats

Using 31p-NMR (the phosphorus nuclear magnetic resonance) spectroscopy, we measured intracellular free Mg levels in the erythrocytes of untreated (n = 7) and diltiazem-treated spontaneously hypertensive rats (SHR) (n = 8), and compared them with age-matched Wistar-Kyoto rats (WKY) (n = 10). The intracellular free Mg levels were significantly (p less than 0.01) decreased in untreated SHR compared with those in control WKY. A successful antihypertensive treatment with diltiazem increased the intracellular free Mg levels compared with untreated SHR (p less than 0.05). Furthermore, an inverse correlation was observed between intracellular free Mg levels and blood pressure levels in all groups (r = -0.48, p less than 0.01, n = 25). These observations suggest that abnormalities of intracellular Mg metabolism may be, in part, related to the development or the maintenance of hypertension in SHR.     

Ovariectomy-induced changes in the adrenal cortex of spontaneously hypertensive rats.

Many lines of evidence indicate that adrenocortical steroid hormones are involved in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). Twenty-eight days after ovariectomy a notable decrease in the sistolic blood pressure (BP) was found in SHR, along with a marked atrophy of their adrenal cortices. The hypothesis is advanced that the ovariectomy-induced lowering in BP in SHR may be, at least partly, mediated by the suppression of the adrenal secretory activity, due to the lack of circulating estrogens, which are well known to stimulate hypophyseal ACTH release.     

Nifedipine-resistant Ca(++)-induced contraction in tail artery of spontaneously hypertensive rats.

Nifedipine-resistant Ca(++)-induced contractions (NR-Ca(++)-contraction) were compared in the tail arteries from SHRs and WKYs (5 and 13 week old). NR-Ca(++)-contraction of tail artery was defined as follows: Ca(++)-induced contraction in the presence of norepinephrine (NE) (10(-5) M) or 5-hydroxytryptamine (5-HT) (10(-5) M) in Ca(++)-free medium containing EGTA (0.1 mM) and nifedipine (10(-6) M). NR-Ca(++)-contractions in arteries from 5 week old SHRs and WKYs were not different. In contrast, NR-Ca(++)-contractions in arteries from 13 week old SHRs were about 2-fold greater than in arteries from 13 week old WKYs. In arteries from 13 week old WKYs and SHRs, nitroglycerin (10(-5) M) significantly reduced the NR-Ca(++)-contraction in the presence of 5-HT but not in the presence of NE. The reduction was inhibited by the presence of methylene blue (3 x 10(-6) M). 8-Bromo-cGMP (10(-4) M) reduced significantly the NR-Ca(++)-contraction in the presence of 5-HT in arteries from 13 week old SHRs and WKYs. The present experiments clearly demonstrated that the NR-Ca(++)-contractions (both in the presence of NE and 5-HT) in 13 week old SHRs were significantly greater than those in arteries from 13 week old WKYs. These results suggest that in addition to an increase in voltage-operated Ca++ mobilization reported by others, an increase in NR-Ca++ mobilization may contribute to the development of hypertension in SHR.     

Narcotic antagonist-induced hypotension in the spontaneously hypertensive rat

Intravenous naloxone or naltrexone produced transient, dose-related reductions in the mean arterial pressure (MAP) and heart rate (HR) of urethane-anesthetized spontaneously hypertensive rats (SHRs). Yet these same doses of narcotic antagonists reduced HR but not MAP of normotensive Wistar-Kyoto rats (WKYs). Such effects were not observed upon administration to SHRs of increasing doses of methylnaltrexone, which possesses no central activity. (+)-Naloxone, which does not block opiate receptors, reduced HR but not MAP of both SHRs and WKYs. These findings indicate that SHRs and WKYs differ in their MAP and HR responses to narcotic antagonists. The high doses required for effect plus the brevity of the responses suggest that these drug effects are perhaps not mu-opiate receptor-mediated; however, the methylnaltrexone and (+)-naloxone findings clearly implicate a central specificity of action. We conclude that narcotic antagonist-induced changes in MAP and HR in SHRs are possibly specific and central in origin yet not mediated by mu-opiate receptors.     

Acetaldehyde depresses myocardial contraction and cardiac myocyte shortening in spontaneously hypertensive rats: role of intracellular Ca2+.

Acetaldehyde (ACA), the major metabolite of ethanol, exerts both stimulatory and depressive actions on myocardial tissue. We have recently shown that ACA depresses myocardial contraction, cardiac myocyte shortening and intracellular Ca2+ transients in normal rat heart. The purpose of the present study was to determine the influence of hypertension on ACA-induced myocardial actions. Mechanical properties of left ventricular papillary muscles and ventricular myocytes isolated from both 25-week-old normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were evaluated using force-transducer and video edge-detection, respectively. Papillary muscles and cardiac myocytes were electrically stimulated to contract at 0.5 Hz. Contractile properties analyzed include: peak tension development (PTD), peak twitch amplitude (PTA), time-to-PTD/PTA (TPT/TPS), time-to-90% relaxation/relengthening (RT90/TR90) and maximal velocities of contraction/shortening and relaxation/relengthening (+/-VT/+/-dL/dt). Intracellular Ca2+ transients were measured as fura-2 fluorescence intensity (FFI) changes. ACA (1-30 mM) depressed PTD without affecting other mechanical indices in both WKY and SHR myocardium, with maximal inhibition of 64 and 69%, respectively. SHR myocytes exhibited increased cell dimension, baseline PTA and resting intracellular Ca2+ levels, compared to WKY counterparts. ACA (0.03-30 mM) depressed PTA without affecting TPT, TR90 and +/-dL/dt. The maximal inhibitions were 31 and 36% in WKY and SHR groups, respectively. Interestingly, ACA exerted a biphasic effect on FFI, displaying potentiation at lower doses (<3 mM) and inhibition at higher doses (>3 mM). The maximal increase in FFI changes were 19 and 22% at 0.3 mM and the maximal decreases were 37 and 29% at 30 mM ACA, in WKY and SHR myocytes, respectively. Neither resting intracellular Ca2+ levels (FFI) nor fluorescence decay time (FDT) were affected by ACA. The increase in FFI was attenuated by propranolol (1 microM), whereas the decrease in FFI was reversed by BayK 8644 (1 microM). These results suggest that hypertension does not appear to alter ACA-induced myocardial depression. The mechanism underlying ACA-induced myocardial actions may involve increased beta-adrenergic activity at low doses and reduced Ca2+ entry and/or release at high doses.     

Depressor effect of diabetes in the spontaneously hypertensive rat: associated changes in heart performance

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar-Kyoto (WK) and Sprague-Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/mu LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV-dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and -dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV-dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intensified mouse killing in the spontaneously hypertensive rat

After one week in isolation spontaneously hypertensive male rats killed mice more frequently than did normal Wistar Controls, 70 vs 20%. Hypertensive killers had a somewhat lower blood pressure than did hypertensive non-killers. Retest after one hour demonstrated slower recognition time, decreased killing and increased kill time for normotensive killer rats. Mouse killing increased among hypertensive rats, and they became more proficient as evidenced by decreased kill time.     

Differential changes in atrial natriuretic peptide and vasopressin receptor bindings in kidney of spontaneously hypertensive rat

To elucidate the role of atrial natriuretic peptide (ANP) and vasopressin (VP) in a hypertensive state, ANP and VP receptor bindings in spontaneously hypertensive rat (SHR) kidney were analyzed using the radiolabeled receptor assay (RRA) technique. Systolic blood pressure of SHR aged 12 weeks was statistically higher than that of age-matched Wistar Kyoto (WKY) rats. Maximum binding capacity (Bmax) of [125I]-ANP binding to the SHR kidney membrane preparations was statistically lower than that of WKY rats, but dissociation constant (Kd) was not significantly different. On the other hand, Bmax of [3H]-VP binding to the SHR kidney membrane preparations was statistically higher than that of WKY rats, but Kd were similar. Since the physiological action of ANP is natriuresis and VP is the most important antidiuretic hormone in mammalia, these opposite changes of ANP and VP receptor bindings in SHR kidney suggested that these peptides may play an important role in the pathophysiology of the hypertensive state, although it has not been confirmed as yet.     

Mapping genes controlling hematocrit in the spontaneously hypertensive rat

The genes that determine the baseline hematocrit level in humans and experimental animals are unknown. The spontaneously hypertensive rat (SHR), the most widely used animal model of human essential hypertension, exhibits an increased hematocrit when compared with the normotensive Brown Norway (BN-Lx) strain (0.54 ± 0.02 vs. 0.44 ± 0.02, p < 0.01). Distribution of hematocrit values among recombinant inbred (RI) strains derived from SHR and BN-Lx progenitors was continuous, which suggests a polygenic mode of inheritance. The narrow heritability of the hematocrit was estimated to be 0.32. The Eno2 marker on Chromosome (Chr) 4 showed the strongest association (p < 0.0001) with the observed variability of hematocrit among RI strains. The erythropoietin (Epo) gene, originally reported to be syntenic with Eno2, has been mapped to Chr 12, thus excluding it as a potential candidate gene for the increased hematocrit in the SHR. The current linkage data extend homologies between rat, mouse, and human chromosomes. Received: 11 December 1996 / Accepted: 17 February 1997     

Properties of ventricular myocytes isolated from the hypertrophied and failing hearts of spontaneously hypertensive rats.

OBJECTIVE: To investigate how the morphological and physiological properties of single myocytes isolated from the hypertrophied, failing left ventricles (LV) differ from those of normal or hypertrophied not failing ventricles. METHOD: Single myocytes were isolated separately from right (RV) and left ventricles (LV) of male spontaneously hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats at the age of 6 and 12 months and of SHRs which developed or not developed heart failure at the age of 20-24 months. We measured cells dimensions, range and kinetics of electrically stimulated or initiated by caffeine contractions and Ca2+ transients, and investigated the response of cells to thapsigargin. RESULTS: The transversal dimensions of the LV myocytes of 6 months old SHRs showed approximately 20% increase with respect to transversal dimensions of their RV myocytes and LV and RV myocytes of WKY rats. The difference did not change with progressing age and in the heart failure. The LV myocytes of 6 or 12 months old SHRs showed slowed kinetics of the Ca2+ transients and of contraction and relaxation and decreased contractile response to 2 s superfusion with 15 mM caffeine preceded by 5 mM Ni2+ used as an index of the sarcoplasmic reticulum (SR) Ca2+ content. Despite of this the range of shortening and relative contribution of the SR to contraction (assessed by measuring of the residual contractile response to electrical stimulation in cells poisoned with thapsigargin) or relaxation (assessed by calculation of the ratio of rate constants of the electrically stimulated and stimulated by 30 s superfusion with caffeine Ca2+ transients) was not altered in the hypertrophied myocytes. Properties of the LV myocytes of the 20-24 old SHRs with or without heart failure did not differ from those of LV myocytes of younger SHRs. The contractile response to caffeine of their RV myocytes dropped to the level of that in the LV myocytes. CONCLUSION: Our results suggest that transition from the compensated hypertrophy to the heart failure in 20-24 months old SHRs did not result from the further changes in properties of the surviving myocytes. Data from literature suggest that myocyte apoptosis and remodeling of the extramyocyte space is the more likely reason.