Myosin Isozymes Research Articles

Thyroid state and tolerance of mammalian myocardium to hypoxia

Thyroid hormone is known to affect myocardial glycogen stores and thereby possibly limit anaerobic performance of mammalian cardiac muscle. Thyroid hormone administration (3,5,3'-triiodo-L-thyroxine, 300 microg/kg/day, sc) for 10 days decreased left ventricle (LV) glycogen concentration relative to euthyroid animals (2.78+/-0.46 vs. 4.28+/-0.29 mg/g of LV (mean+/-SEM)) while increasing the percent of V(1) myosin isozyme, contractile activity and cardiac mass. In contrast, thyroidectomy increased myocardial glycogen stores (8.50+/-0.56 mg/g of LV) and shifted the myosin isozyme toward V(3), prolonged contractile activity and decreased LV mass. Thyroxine administration for 3, 7 and 10 days to thyroidectomized animals progressively decreased contractile duration and increased LV mass. Thyroxine administration for 3 or 7 days to thyroidectomized rats did not reduce glycogen stores (7.75+/-1.02 and 9.62+/-1.16 mg/g of LV, respectively), whereas myocardial glycogen declined to 3.30+/-0.58 mg/g of LV after 10 days of treatment. During hypoxia, cardiac muscle from thyroidectomized rats maintained greater active force and developed less contracture relative to euthyroid and, to a greater extent, than hyperthyroid rats. Removal of glucose from the bath decreased anaerobic performance and impaired recovery; however, myocardium from thyroidectomized rats remained more tolerant to hypoxia than the euthyroid group. Overall, the intrinsic LV glycogen content was positively correlated to anaerobic performance. These data demonstrate that the thyroid state profoundly affects myocardial growth, contractility and anaerobic performance of rat myocardium. Although energy demand may affect function during hypoxia, anaerobic substrate reserve (cardiac glycogen concentration) appears to be the primary factor determining tolerance to hypoxic stress.

Identification and Characterization of an 8-kDa Light Chain Associated with Dictyostelium discoideum MyoB, a Class I Myosin

Dictyostelium discoideum MyoB is a single-headed class I myosin. Analysis of purified MyoB by SDS-PAGE indicated the presence of an approximately 9-kDa light chain. A tryptic digest of MyoB yielded a partial sequence for the light chain that exactly matched a sequence in a 73-amino acid, 8,296-Da protein (dictyBase number DDB0188713). This protein, termed MlcB, contains two EF-hand motifs and shares approximately 30% sequence identity with the N- and C-terminal lobes of calmodulin. FLAG-MlcB expressed in Dictyostelium co-immunoprecipitated with MyoB but not with the related class myosins and MyoD. Recombinant MlcB bound Ca2+ with a Kd value of 0.2 microm and underwent a Ca2+-induced change in conformation that increased alpha-helical content and surface hydrophobicity. Mutational analysis showed that the first EF-hand was responsible for Ca2+ binding. In the presence and absence of Ca2+ MlcB was a monomer in solution and bound to a MyoB IQ motif peptide with a Kd value of approximately 0.5 microm. A MyoB head-neck construct with a Ser to Glu mutation at the TEDS site bound MlcB and displayed an actin-activated Mg2+ ATPase activity that was insensitive to Ca2+. We conclude that MlcB represents a novel type of small myosin light chain that binds to IQ motifs in a manner comparable with a single lobe of a typical four-EF-hand protein.

'Artificial' myosin isozymes: preparation and characteristics.

Using precisely monitored proteolytic digestion conditions rabbit fast skeletal muscle myosin could be selectively modified in different ways. A myosin isozyme with a 20-kDa alkali light chain 1 (A1) could be obtained by digesting with papain in the presence of Ca2+. Under these conditions alkali light chain 2 (A2) was cleaved at Lys-17 and lost a 2.3-kDa N-terminal fragment including the strongly basic N terminus and about half of the characteristic (Ala-Pro) sequence. The Nbs2-[5,5' dithiobis(2-nitrobenzoic acid)-]light chain and A2 were left unmodified and less than 5% of the myosin heavy chain presented a break in the subfragment-2 region. EDTA and Ca2+ ATPase activities were unchanged. A myosin isozyme with an 18-kDa Nbs2-light chain was obtained by limited digestion with trypsin in the presence of Ca2+. The 18.9 leads to 18-kDa conversion was nearly 100% whereas less than 10% of the heavy chain was fragmented and only about 5% of A1 was converted to A1. The Nbs2-light chain was cleaved at Arg-7 preserving Ser-15 and consequently a phosphorylated modified myosin could be obtained. A quasi-elastic light-scattering study showed that this modified myosin in high-ionic-strength solutions exhibited physicochemical characteristics quite similar to those of unmodified myosin.

Myosin-1c, the hair cell's adaptation motor.

Given their prominent actin-rich subcellular specializations, it is no surprise that mechanosensitive hair cells of the inner ear exploit myosin molecules-the only known actin-dependent molecular motors-to carry out exotic but essential tasks. Recent experiments have confirmed that an unconventional myosin isozyme, myosin-1c, is a component of the hair cell's adaptation-motor complex. This complex carries out slow adaptation, provides tension to sensitize transduction channels, and may participate in assembly of the transduction apparatus. This review focuses on the detailed operation of the adaptation motor and the functional consequences of the incorporation of this specific myosin isozyme into the motor complex.

Age-related differences in the effect of running training on cardiac Myosin isozyme composition in rats.

We examined the effect of running training on age-related changes in cardiac myosin isozyme composition in rats. Female Fischer 344 rats (6, 12, 20, and 27 months old) were divided into two groups: sedentary control and trained. The trained group rats were trained by treadmill running for up to 60 minutes per day, 5 days per week for 8 weeks at up to 30 m per minute. In sedentary control rats, the proportion of V1 myosin, that is, alpha-myosin heavy chain (MyHC) isoform, decreased progressively from 6 to 27 months of age. In the younger age groups (6 or 12 months old), there was a shift from V1 myosin to V3 myosin (beta-MyHC isoform) in trained hearts. However, the training program did not induce a cardiac myosin isozyme transition in older rats (20 or 27 months old). These results suggest that the mechanisms mediating the responses of cardiac muscle to running training alter during aging.

Changes in thiol reactivity and extractability of myofibril bound cardiac troponin C in porcine malignant hyperthermia.

We recently showed that a shift ( approximately 44%) in cardiac myosin isozyme from V3 to V1 occurs in the hearts of malignant hyperthermia (MH)-susceptible pigs and may be important in the disease. To follow up this finding, we investigated whether this myosin isozyme shift results in conformational changes in cardiac troponin C (cTnC). The two cysteine residues (Cys-35 and Cys-84) in the regulatory domain of cTnC make it possible to attach conformational probes to this region. Incorporation of a fluorescent probe, 7-diethylamino-3-(4'maleimidylphenyl)-4-methylcoumarin (CPM), into myofibril-bound cTnC was measured by alkaline urea gel electrophoresis, followed by quantification of the protein and the fluorescent label on the gels. The structural stability of cTnC incorporated into cardiac myofibrils was compared between normal and MH-susceptible pigs by selective cTnC extraction and re-incorporation. Changes were detected in both the reactivity of cTnC with CPM in rigor myofibrils and cTnC incorporation into myofibrils from the hearts of MH-susceptible pigs. These changes are very likely to be a consequence of the cardiac myosin isozyme shift in the hearts of MH-susceptible pigs, which may contribute to the changes in the myofilament response to Ca(2+) binding and to the modulation of cardiac contractility seen in this disease.

Characterization of sucrose-induced changes in cardiac phenotype.

The neuroendocrine factors responsible for long-term regulation of cardiac contractile performance remain ill defined. We examined influences of diet on the expression of myosin isozymes, sarcoplasmic reticulum (SR) Ca(2+) uptake and serum parameters. Dietary regimens (ad libitum feeding, intermittent fasting and 32% sucrose feeding) were used to alter the neurohumoral status of rats. Intermittent fasting decreased serum insulin levels ( P<0.05) and was associated with decreased SR Ca(2+) uptake and myosin V1 proportion ( P<0.05). Sucrose (32%) feeding increased myosin V1 of fasted and ad libitum fed rats ( P<0.05) but had no effect on insulin or SR Ca(2+) uptake. Expression of the alpha-myosin heavy chain correlated with serum insulin. Treatment of sucrose-fed rats with the sympatholytic compound moxonidine and the hypoglycaemic compounds BM13.907 and ciglitazone partially prevented the increase in myosin V1 ( P<0.05) but had no effect on SR Ca(2+) uptake and insulin. The data show that adrenergic activity and metabolic signals are important for an increase in myosin V1 in sucrose-fed rats, which can be associated with an unaltered SR Ca(2+) uptake rate.

03 Modification of myosin isozyme gene expression in heart failure by blockade of the renin-angiotensin system

03 Modification of myosin isozyme gene expression in heart failure by blockade of the renin-angiotensin system

Myosin-I isozymes in neonatal rodent auditory and vestibular epithelia.

Myosin isozymes are essential for hair cells, the sensory cells of the inner ear. Because a myosin-I subfamily member may mediate adaptation of mechanoelectrical transduction, we examined expression of all eight myosin-I isozymes in rodent auditory and vestibular epithelia. Using RT-PCR, we found prominent expression of three isozymes, Myo1b (also known as myosin-Ia or myr 1). Myo1c (myosin-Ib or myr 2). and Myo1e (myr 3). By contrast, Myo1a (brush-border myosin-I), Myo1d (myosin lg or myr 4). Myo1f, Myo1g, and Myo1h were less readily amplified. Because sequence analysis demonstrated that the RT-PCR products encoded the appropriate isozymes, this represents the first demonstration of expression of all eight mouse myosin-I genes. Using immunocytochemistry with isozyme-selective antibodies, we found that Myo1b was located at apical surfaces of supporting cells that surround hair cells in auditory epithelia of postnatal rats. In vestibular epithelia, Myo1b was present in a ring within the apical pole of the hair cell. In both cases, expression was prominent only immediately after birth. Myo1e was found in hair cells of the auditory and vestibular epithelia; this isozyme was enriched in the cuticular plate, the actin meshwork that anchors the stereocilia. Myo1c was found in hair-cell stereocilia, concentrated towards their tips; we confirmed this localization by using adenovirus vectors to direct expression of a GFP-Myo1c tail fusion protein; this fusion protein localized to plasma membranes, often concentrating at stereociliary tips. Myo1c therefore remains the myosin isozyme best localized to carry out transducer adaptation.

Attenuation of Ca 2+-activated ATPase and shortening velocity in hypertrophied fast twitch skeletal muscle from aged Japanese quail

The effect of aging on the in vitro contractile properties of the patagialis (PAT) muscle of 35 young adult (YA; 8 weeks of age) and 35 aged adult (AA, 110 weeks of age) Coturnix quails was examined after 0–30 days of stretch-overload. Overload was achieved by placing a weight equivalent to 12% of the birds' body weight on one wing. The contralateral wing served as the intra-animal control. Overload increased the weight of the PAT by 45.1±2.1% in YA, and 24.1±2.6% in AA. Twitch contraction time increased with loading from 43.2±1.2 to 67.3±2.2 ms in YA birds and 57.2±1.7 to 77.4±1.9 ms in AA birds. Unloaded shortening velocity (Vo) decreased by 40.1±2.2 and 38.8±3.2% in YA and aged birds, respectively. The decrease in fast myosin expression was greater in overloaded muscles of YA (20%) as compared to AA birds (12%). However, this was accompanied by a greater decrease in total muscle ATPase activity in aged birds (61%) compared to YA birds (40%). Myosin isozyme Ca 2+-ATPase activity was 26% lower in FM1 but not other fast myosins in YA birds, but it was ∼30% lower in all fast myosins in PAT muscles of aged birds. These data show that the reduction of Vo and the increase in twitch duration with aging may be due in part to reductions in ATPase activity in all myosin isoforms, as compared to myosin isoforms isolated from YA birds.

Cyclical changes in high-energy phosphates during the cardiac cycle by pacing-Gated 31P nuclear magnetic resonance.

Whether cyclical changes in energy-related phosphate metabolites arise during a cardiac cycle in isolated rat hearts and are affected by differences in myosin isozyme composition was determined. Myocardial adenosine triphosphate (ATP), phosphocreatine (PCr), inorganic phosphate (Pi), and intracellular pH in normal, hypothyroid and hyperthyroid rat hearts were measured using the pacing-gated 31P nuclear magnetic resonance technique. Maximal decrease in ATP and PCr, and maximal increase in Pi at the peak-systole in normal rat hearts were observed. In hypothyroid and hyperthyroid rats, similar cyclical changes in phosphate metabolites were observed during the cycle. However, the magnitude of fluctuations was smaller in hypothyroid rats and larger in hyperthyroid rats compared with that observed in normal rats. Cardiac myosin isozyme patterns were also different amongst the experimental groups. The results suggest that cyclical changes and the magnitude of fluctuations in energy-related phosphate metabolites during a cardiac cycle may depend on the cardiac workload and the intrinsic properties in the enzyme kinetics of myosin.

Sarcoplasmic reticulum function and carnitine palmitoyltransferase-1 inhibition during progression of heart failure.

Failing cardiac hypertrophy is associated with an inadequate sarcoplasmic reticulum (SR) function. The hypothesis was examined that pressure overloaded hearts fail to increase SR Ca(2+) uptake rate proportionally to the hypertrophy and that carnitine palmitoyltransferase-1 inhibition by etomoxir ((+/-)-ethyl 2[6(4-chlorophenoxy)hexyl] oxirane-2-carboxylate) can counteract this process. Severe left ventricular pressure overload was induced in rats by constricting the ascending aorta for 8, 10, 14 and 28 weeks leading to cardiac hypertrophy (+62 - +103% of sham-operated rats) and pulmonary congestion. Homogenate oxalate-facilitated SR Ca(2+) uptake rate g wet wt(-1) was reduced (P<0.05) by 29.9+/-1.8% irrespective of phospholamban phosphorylation (in the presence of catalytic subunit of protein kinase A) and inhibition of SR Ca(2+) release channel by ruthenium red. SERCA2 protein level was reduced (P<0.05) by 30.4+/-0.8%. SR Ca(2+) uptake rate was inversely correlated (P<0.05) with left ventricular weight but was not affected by the occurrence of pulmonary congestion. Because SR Ca(2+) uptake rate of whole ventricles was not reduced, a hypertrophy proportional dilution of SR Ca(2+) uptake has to be inferred which precedes pulmonary congestion. Treatment with etomoxir (15 mg kg body wt(-1) day(-1) for 10 weeks) did not affect left ventricular weight but decreased (P:<0.05) the right ventricular hypertrophy related to pulmonary congestion. In parallel, SR Ca(2+) uptake rate of left ventricle and myosin isozyme V(1) were increased (P<0.05). Etomoxir represents a candidate approach for prevention of heart failure by inducing a hypertrophy proportional increase in SR Ca(2+) uptake rate.

Altered Expression of Cardiac Myosin Isozymes Associated with the Malignant Hyperthermia Genotype in Swine

Anesthetic-induced malignant hyperthermia (MH) in humans and pigs is associated with dramatic alterations in cardiac function. However, it remains controversial as to whether MH-associated cardiac symptoms represent a primary difference of myocardium or a secondary alteration consequent to increases in the hyperthermic stress. Here the authors describe changes in myosin isoform expression in the hearts of MH-susceptible pigs with and without prior exposure to halothane. One group of pigs was diagnosed as MH susceptible by halothane challenge and Hal-1843 nucleotide examination. To determine if there is an effect of halothane exposure, another group of pigs was diagnosed by simple MH genotyping without exposure to halothane. After diagnosis and genotyping, animals with and without exposure to halothane were killed to study cardiac myosin isozyme distributions, cardiac myofibrillar adenosine triphosphatase (ATPase) activity, and the steepness of the Ca2+-ATPase activity relation in the hearts of normal and susceptible pigs. The altered myosin isozyme expression was analyzed by pyrophosphate gel electrophoresis. Malignant hyperthermia-susceptible animals with the prior halothane challenge showed an increased V1 myosin (-44%) expression, increased myofibrillar ATPase activity (-25%) and increased steepness of the Ca2+-ATPase activity relation. Without exposure to halothane, no change of myofibrillar ATPase activity was found in the hearts of different genotyped pigs, but there was a small increase in expression of V1 myosin (-5%) in the mutant (TT). The potential modulation of V1 myosin expression occurs in the hearts of MH-susceptible pigs. The added stress by halothane challenge would further cause a V3 --> V1 shift, which may be attributed to the long-term effects of hyperthermic stress.

Physiology of a microgravity environment invited review: microgravity and skeletal muscle.

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

The roles of unconventional myosins in hearing and deafness.

The proper expression and function of several unconventional myosins are necessary for inner-ear function. Mutations in MYO7A and MYO15 cause deafness in humans, and mice. Whereas mutations in Myo6 cause inner-ear abnormalities in mice, as yet no human deafness has been found to the result of mutations in MYO6. In the mammalian inner ear there are at least nine different unconventional myosin isozymes expressed. Myosin 1 beta, VI, VIIa and probably XV are all expressed within a single cell in the inner ear, the hair cell. The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap. This suggests that these myosins all have unique functions and that all are individually targeted within the hair cell. The mouse is proving to be a useful model organism for studying both human deafness and elucidating the normal functions of unconventional myosins in vivo.

ラット心筋の局所的ミオシンアイソザイム構成比に及ぼすランニングトレーニングの影響

We examined the effect of running training on regional cardiac myosin isozyme composition in rats. Male Sprague-Dawley strain rats (4 weeks old) were used, and divided into two groups: sedentary control (C) and trained (T) groups. The T group was trained by treadmill running (40 m/min, 1h/day, 5 days/week, for 12 weeks) . At 16 weeks old, their hearts were excised. The left ventricle was separated into the subendocardium (Endo) and subepicardium (Epi) by dissecting the ventricle at the mid-wall. The ventricular myosin isozymes were examined by electrophoresis on pyrophosphate gel under non-dissociating conditions. The results showed the following: 1) The relative heart weight of the T group was significantly higher than the C group. 2) Left ventricular myosin isozyme composition showed a region-specific distribution in the C rats, and the proportion of V3 myosin or β-myosin heavy chain in the Endo was significantly higher than that of the Epi. However, the training had no effect on the cardiac myosin isozyme in either portion. 3) The activity of citrate synthase did not show transmural gradient in the ventricle of C animals. Training had no effect on the activities of either portion. 4) The activity of lactate dehydrogenase (LDH) showed transmural gradient in the ventricle of C rats. Training-induced changes in the activity of LDH were found in both portions, therefore, training abolished the transmural gradient in the activity of LDH, suggesting a corresponding redistribution of the myocardial work load.These results indicate that running training might induce the redistribution of the myocardial work load, whereas the stimulation apparently has no effect on the regional distribution of cardiac myosin isozyme composition.

Lack of Effect of Running Training at Two Intensities on Cardiac Myosin Isozyme Composition in Rats.

Little information is available regarding the influence of the intensity of endurance training over biochemical profiles in cardiac muscle. We assessed the effect of running training at two different intensities on cardiac myosin isozyme composition in rats. Male Sprague-Dawley rats (4 weeks old) were divided into four groups: sedentary control (SC), trained at 20 m/min (T20), trained at 40 m/min (T40), and weight-matched sedentary control (WMSC) groups. The T20 and T40 group rats were trained by treadmill running for 60 min/d, 5 d/week at 20 or 40 m/min, respectively, for 11 to 12 weeks. In both groups the left ventricle was significantly heavier than in WMSC animals. The ratio of left ventricle weight to body weight was significantly greater in T40 rats than in either the untrained (SC and WMSC) or trained T20 rats. Thus the extent of exercise-induced cardiac hypertrophy appears to be influenced by the intensity of running training. However, neither of the training programs (1) induced a change in cardiac myosin isozyme composition or (2) had any effect on myocardial succinate dehydrogenase or citrate synthase activity. These results suggest that although the intensity of running training may play an important role in cardiac morphological adaptation, it does not modulate the cardiac biochemical adaptation to running training.

Radiotelemetric characterization of overweight-associated rises in blood pressure and heart rate.

We addressed the hypothesis that hypercaloric diets induce hyperkinetic hypertension irrespective of day-night cycle and locomotor activity that is associated with altered cardiac myosin isozymes. Normotensive rats with implanted radiotelemetry pressure transducers were fed increasing amounts of coconut fat (8, 16, and 24%, each for 2 wk) corresponding to 20-47% of total calories from fat. Thereafter, increasing amounts of sucrose (16, 32, and 50%) and fructose (50%) were added to the 24% fat diet corresponding to 13-40% of total calories from sugar. In contrast to the fat diets, the 32% and 50% sucrose diets as well as the 50% fructose diets increased (P < 0.05) blood pressure (systolic maximum +13 mmHg, diastolic maximum +4 mmHg, mean maximum +7 mmHg) and heart rate (maximum +50 beats/min) irrespective of the day-night cycle and the unaltered locomotor activity. Furthermore, body weight increased (P < 0.05) during the 32% and 50% sucrose feedings. The increased blood pressure and heart rate normalized after rats were fed a regular chow. We concluded that an excessive caloric intake results in hyperkinetic hypertension that increases the myosin V(1) proportion.

ATP-Induced Ca2+ Release in Cochlear Outer Hair Cells: Localization of an Inositol Triphosphate-Gated Ca2+ Store to the Base of the Sensory Hair Bundle

We used a high-performance fluorescence imaging system to visualize rapid changes in intracellular free Ca(2+) concentration ([Ca(2+)](i)) evoked by focal applications of extracellular ATP to the hair bundle of outer hair cells (OHCs): the sensory-motor receptors of the cochlea. Simultaneous recordings of the whole-cell current and Calcium Green-1 fluorescence showed a two-component increase in [Ca(2+)](i). After an initial entry of Ca(2+) through the apical membrane, a second and larger, inositol triphosphate (InsP(3))-gated, [Ca(2+)](i) surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca(2+) release site showed that it coincides with the localization of a unique system of endoplasmic reticulum (ER) membranes and mitochondria known as Hensen's body. Using confocal immunofluorescence microscopy, we showed that InsP(3) receptors share this location. Consistent with a Ca(2+)-mobilizing second messenger system linked to ATP-P2 receptors, we also determined that an isoform of G-proteins is present in the stereocilia. Voltage-driven cell shape changes and nonlinear capacitance were monitored before and after ATP application, showing that the ATP-evoked [Ca(2+)](i) rise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca(2+)-clearance power of the stereocilia and transiently elevates [Ca(2+)](i) at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and potentially influence mechanotransduction.

Age-related difference in cardiac adaptation to chronic hypertension in rats, with and without nifedipine treatment.

Three myosin isozymes, V1 (alphaalpha MHC = Myosin Heavy Chain gene), V2 (alphabeta MHC) and V3 (betaalpha MHC) that are identified in the cardiac ventricles of most mammals have been shown to shift to a V3 predominance pattern during cardiac growth and in response to left ventricular pressure overload, and to V1 predominance following anti hypertensive treatment. This study examined whether long-term hypertension impairs the ability of the adult heart to restructure myosin isozyme proportions. Using pyrophosphate gel electrophoresis, we studied proportions of cardiac myosin isozymes (V1 and V3) in young (16 weeks) and adult (36 weeks) spontaneously hypertensive rats (SHR), and following 12 weeks of nifedipine (N) treatment in age-matched SHR rats (SHR-N). The values of V1 and V3 myosin isozymes were derived by adding half of the value of V2 to each isozyme proportion. The V3 proportion in the young SHR control (SHR-C) group (49%) was 34% higher (p < 0.05) than in the young Wistar Kyoto control (WKY-C) group (37%). However, the proportion was similarly high, though not statistically significant, in both the adult SHRC (73%) and WKY-C (71%) groups. The proportion in the young SHR-N group (29%) was 41% lower (p < 0.05) than in the young SHR-C group (49%), and the proportion in the adult SHR-N group (47%) was 34% lower (p < 0.05) than in the adult SHR-C group (73%). The ratio of left ventricular weight to body weight (LVW/BW), which determines left ventricular hypertrophy (LVH), was higher in both young and adult SHR-C (26%, p < 0.05, and 42%, p < 0.05, respectively) than in WKY-C groups. The mean LVW/BW was 27% (p < 0.05) greater in adult than in young SHR-C rats. The LVW/BW in both age groups of treated SHR-N was similar to that in age matched WKY-C rats. Our study showed that a rise in the V3 level occurs in young hypertensive rats, but no rise occurs in the V3 level in adult hypertensive rats. High blood pressure seems to contribute to the high V3 level in young hypertensive rats, but in adult hypertensive rats, high blood pressure does not accentuate the V3 rise already acquired due to the aging process. Nifedipine treatment in both young and adult hypertensive rats prevented the V3 rise due to hypertension and to the aging process. This effect of nifedipine seems to be through its antihypertensive action.