ryanodine and Body-Weight

Although the beneficial effects of resistance training (RT) on the cardiovascular system are well established, few studies have investigated the effects of the chronic growth hormone (GH) administration on cardiac remodeling during an RT program.. To evaluate the effects of GH on the morphological features of cardiac remodeling and Ca2+ transport gene expression in rats submitted to RT.. Male Wistar rats were divided into 4 groups (n = 7 per group): control (CT), GH, RT and RT with GH (RTGH). The dose of GH was 0.2 IU/kg every other day for 30 days. The RT model used was the vertical jump in water (4 sets of 10 jumps, 3 bouts/wk) for 30 consecutive days. After the experimental period, the following variables were analyzed: final body weight (FBW), left ventricular weight (LVW), LVW/FBW ratio, cardiomyocyte cross-sectional area (CSA), collagen fraction, creatine kinase muscle-brain fraction (CK-MB) and gene expressions of SERCA2a, phospholamban (PLB) and ryanodine (RyR).. There was no significant (p > 0.05) difference among groups for FBW, LVW, LVW/FBW ratio, cardiomyocyte CSA, and SERCA2a, PLB and RyR gene expressions. The RT group showed a significant (p < 0.05) increase in collagen fraction compared to the other groups. Additionally, the trained groups (RT and RTGH) had greater CK-MB levels compared to the untrained groups (CT and GH).. GH may attenuate the negative effects of RT on cardiac remodeling by counteracting the increased collagen synthesis, without affecting the gene expression that regulates cardiac Ca2+ transport.

Topics: Animals; Body Weight; Calcium; Calcium-Binding Proteins; Collagen; Creatine Kinase, BB Form; Gene Expression; Growth Hormone; Heart Ventricles; Male; Myocytes, Cardiac; Organ Size; Polymerase Chain Reaction; Rats, Wistar; Resistance Training; Ryanodine; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Time Factors; Ventricular Remodeling

The effects of ryanodine on twitch contraction and basal tension of oesophageal striated muscle were compared between preparations from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). Ryanodine (3 x 10(-7) M) augmented the twitch contraction in WKY preparations, butt attenuated it in SHRSP preparations. Rates of contraction and relaxation of twitch contraction, normalized to developed tension, were slightly decreased by ryanodine in both preparations. The effect of ryanodine was not different between WKY and SHRSP preparations. Ryanodine elevated the basal tension in WKY preparations but not in SHRSP preparations. Ryanodine elevated the intracellular Ca(2+) level in both preparations, but the response was significantly less in SHRSP preparations. Resting and action potentials were not significantly different between WKY and SHRSP preparations, while the duration of the action potential was significantly longer in SHRSP preparations. Ryanodine did not alter the resting and action potentials of either preparation. These results suggest that the Ca(2+) handling properties, including the ryanodine receptor, of the sarcoplasmic reticulum are genetically altered in oesophageal striated muscle of SHRSP.

Topics: Animals; Blood Pressure; Body Weight; Caffeine; Calcium; Esophagus; Hypertension; In Vitro Techniques; Intracellular Fluid; Male; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ryanodine; Species Specificity

To elucidate whether properties of the sarcoplasmic reticulum are altered, not only in vascular smooth muscle, but also in visceral striated muscle of spontaneously hypertensive rats (SHR), caffeine-induced contractures in oesophageal striated muscle of Wistar Kyoto rats (WKY) and stroke-prone SHR (SHRSP) were compared. In both preparations, 30 mM caffeine induced a contracture with two components. The second component, which was diminished by extracellular Ca(2+) removal or Ni(2+) but not by verapamil, was much smaller in SHRSP. Both components and differences between WKY and SHRSP coincided with changes in intracellular Ca(2+). Although membrane potential was identical between these preparations, caffeine induced slight depolarization only in WKY preparations. Similar depolarization was observed with 10 mM K(+), which induced no contraction. It is suggested that the first and the second components of caffeine-induced contracture were induced by Ca(2+) released from sarcoplasmic reticulum and by Ca(2+) that entered through channels activated by sarcoplasmic reticulum Ca(2+) depletion, respectively. In SHRSP preparations, Ca(2+) from the latter pathway was clearly decreased, although this change is thought not to be related to the initiation of hypertension. These results suggest that Ca(2+) handling properties of cell membrane and sarcoplasmic reticulum are generally altered in muscles of SHRSP.

Topics: Animals; Blood Pressure; Body Weight; Caffeine; Calcium; Calcium Channel Blockers; Central Nervous System Stimulants; Esophagus; Hypertension; In Vitro Techniques; Membrane Potentials; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ryanodine; Verapamil

Transgenic mice with cardiac-specific overexpression of active Akt (TG) not only exhibit hypertrophy but also show enhanced left ventricular (LV) function. In 3-4-month-old TG, heart/body weight was increased by 60% and LV ejection fraction was elevated (84 +/- 2%, p < 0.01) compared with nontransgenic littermates (wild type (WT)) (73 +/- 1%). An increase in isolated ventricular myocyte contractile function (% contraction) in TG compared with WT (6.1 +/- 0.2 versus 3.5 +/- 0.2%, p < 0.01) was associated with increased Fura-2 Ca2+ transients (396 +/- 50 versus 250 +/- 24 nmol/liter, p < 0.05). The rate of relaxation (+dL/dt) was also enhanced in TG (214 +/- 15 versus 98 +/- 18 microm/s, p < 0.01). L-type Ca2+ current (ICa) density was increased in TG compared with WT (-9.0 +/- 0.3 versus 7.2 +/- 0.3 pA/pF, p < 0.01). Sarcoplasmic reticulum Ca2+ ATPase 2a (SERCA2a) protein levels were increased (p < 0.05) by 6.6-fold in TG, which could be recapitulated in vitro by adenovirus-mediated overexpression of Akt in cultured adult ventricular myocytes. Conversely, inhibiting SERCA with either ryanodine or thapsigargin affected myocyte contraction and relaxation and Ca2+ channel kinetics more in TG than in WT. Thus, myocytes from mice with overexpressed Akt demonstrated enhanced contractility and relaxation, Fura-2 Ca2+ transients, and Ca2+ channel currents. Furthermore, increased protein expression of SERCA2a plays an important role in mediating enhanced LV function by Akt. Up-regulation of SERCA2a expression and enhanced LV myocyte contraction and relaxation in Akt-induced hypertrophy is opposite to the down-regulation of SERCA2a and reduced contractile function observed in many other forms of LV hypertrophy.

Topics: Adenoviridae; Alkaline Phosphatase; Animals; Blotting, Western; Body Weight; Calcium; Calcium-Transporting ATPases; Calsequestrin; Dose-Response Relationship, Drug; Down-Regulation; Echocardiography; Electrophysiology; Enzyme Inhibitors; Fura-2; Heart Ventricles; Hypertrophy; Inhibitory Concentration 50; Kinetics; Lysophospholipase; Mice; Mice, Transgenic; Muscle Cells; Organ Size; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Rats; Reverse Transcriptase Polymerase Chain Reaction; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Thapsigargin; Time Factors; Transfection; Transgenes; Up-Regulation

Mammalian hearts experience calcium overload during extreme and prolonged hypoxia and the calcium overload may lead to enzyme activation and cell death. Several calcium transport systems were examined in muskrat hearts and compared to those found in rat hearts to determine if there is a species difference that might be related to the muskrats' superior ability to survive hypoxia. Radiolabeled nitredendipine binding was determined in rat and muskrat hearts to estimate the density of voltage gated calcium channels in surface membranes. There were no species differences. Calcium release channel density in the sarcoplasmic reticulum was estimated by the determination of radiolabeled ryanodine binding in muskrat and rat heart SR membranes. No differences were revealed between species. The SR uptake of calcium was measured in SR membranes from the hearts of the two species. No differences were found in the B(max) values, however, the muskrat SR membranes did have a slightly lower K(m) value. There were large species differences in Na(+)/Ca(2+) exchange in SL membranes with the muskrat heart having approximately 3.5 times the transport capacity of rat SL membranes. During hypoxic conditions in which there is extensive ATP depletion leading to [Na(+)](i) accumulation and discharge of cellular membrane potential, the Na(+)/Ca(2+) exchanger may operate in the reverse mode and import calcium into the cell and accelerate hypoxic damage. Prior to reaching this state a robust Na(+)/Ca(2+) exchange would facilitate the maintenance of normal diastolic calcium levels and calcium cycling. Muskrats hearts are hypoxia tolerant by virtue of their ability to reduce metabolic demand and generate ATP anaerobically thus, maintaining a favorable ATP balance. Therefore, the relative overexpression of Na(+)/Ca(2+) exchangers in muskrat hearts may be beneficial in the preservation of contractile function and calcium homeostasis in this freshwater diving mammal.

Topics: Adenosine Triphosphate; Animals; Arvicolinae; Biological Transport; Body Weight; Calcium; Calcium Channel Agonists; Calcium Channels, L-Type; Cell Membrane; Dose-Response Relationship, Drug; Hypoxia; Kinetics; Myocardium; NADH Dehydrogenase; Protein Binding; Rats; Rats, Sprague-Dawley; Ryanodine; Ryanodine Receptor Calcium Release Channel; Sarcolemma; Sarcoplasmic Reticulum; Sodium; Species Specificity; Time Factors

Modifications in the Ca(2+)-uptake and -release functions of the sarcoplasmic reticulum (SR) may be a major component of the mechanisms underlying thyroid state-dependent alterations in heart rate, myocardial contractility, and metabolism. We investigated the influence of hyperthyroid state on the expression and functional properties of the ryanodine receptor (RyR), a major protein in the junctional SR (JSR), which mediates Ca(2+) release to trigger muscle contraction. Experiments were performed using homogenates and JSR vesicles derived from ventricular myocardium of euthyroid and hyperthyroid rabbits. Hyperthyroidism, with attendant cardiac hypertrophy, was induced by the injection of L-thyroxine (200 microg/kg body wt) daily for 7 days. Western blotting analysis using cardiac RyR-specific antibody revealed a significant increase (>50%) in the relative amount of RyR in the hyperthyroid compared with euthyroid rabbits. Ca(2+)-dependent, high-affinity [(3)H]ryanodine binding was also significantly greater ( approximately 40%) in JSR from hyperthyroid rabbits. The Ca(2+ )sensitivity of [(3)H]ryanodine binding and the dissociation constant for [(3)H]ryanodine did not differ significantly between euthyroid and hyperthyroid hearts. Measurement of Ca(2+)-release rates from passively Ca(2+)-preloaded JSR vesicles and assessment of the effect of RyR-Ca(2+)-release channel (CRC) blockade on active Ca(2+)-uptake rates revealed significantly enhanced (>2-fold) CRC activity in the hyperthyroid, compared with euthyroid, JSR. These results demonstrate overexpression of functional RyR in thyroid hormone-induced cardiac hypertrophy. Relative abundance of RyR may be responsible, in part, for the changes in SR Ca(2+) release, cytosolic Ca(2+) transient, and cardiac systolic function associated with thyroid hormone-induced cardiac hypertrophy.

Topics: Animals; Binding, Competitive; Body Weight; Calcium; Calcium Channel Blockers; Cardiomegaly; Heart; Heart Ventricles; Hyperthyroidism; Male; Myocardium; Organ Size; Protein Isoforms; Rabbits; Ryanodine; Ryanodine Receptor Calcium Release Channel; Thyrotropin; Thyroxine; Triiodothyronine

The purpose of the present study was to estimate the development of the inotropic response to low extracellular sodium (LES) during the perinatal period. The effect of LES (35 mmol.L-1) was measured in isolated perfused control and ryanodine-pretreated rat hearts on prenatal day 20 and postnatal days 1, 2, 4, and 7. The effect of LES on the developed force (DF) of control hearts changes significantly day by day: whereas a persisting increase of magnitude of contractions was recorded in the prenatal hearts, this increase was only transient on postnatal day 1 and 2. Starting from day 4, the initial signs of a triphasic response, typical for adult hearts, appeared (an initial increase of DF, followed by a decrease of DF and a rise of resting force, and finally a delayed increase of DF); this trend was more pronounced on day 7. The LES-induced increase of resting force was recorded only in 2-, 4-, and 7-day-old hearts. The negative inotropic effect of ryanodine (10(-6) mol.L-1) was observed already prenatally (60% of the controls) and continued during the whole period of investigation; in contrast, a ryanodine-induced increase of resting force was recorded only postnatally. However, pretreatment with ryanodine abolished the day-by-day changes in the response to LES: in all the hearts studied, the first phase (initial increase of DF) was followed by a severe depression of the magnitude of contractions, together with increased resting force. Our data show significant age-dependent differences in the cardiac contractile response to LES.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Body Weight; Calcium; Carrier Proteins; Female; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Organ Size; Pregnancy; Rats; Rats, Wistar; Ryanodine; Sarcoplasmic Reticulum; Sodium; Sodium-Calcium Exchanger

The pathogenesis of arrhythmogenic transient depolarizations (TDs) was studied by means of electrophysiological and cytochemical methods in normal and hypertrophied left ventricular myocardium of the rat. In hypertrophy induced by administration of 5 mg/kg isoprenaline once daily for 7 days, the myocardial membrane was depolarized, the action potential duration was prolonged and the Vmax was decreased, as compared with those of age-matched normal controls. TDs induced by a train of action potentials could be observed in hypertrophied myocardium, but not in normal control myocardium. Ryanodine completely abolished TDs, but the beta-adrenoceptor agonist noradrenaline and the adenylate cyclase activator forskolin were without effect. In cytochemical studies, the Na+,K(+)-ATPase activity was localized in the sarcolemma, and three times as much reaction product, which appeared on the inner side of the cell membrane, was found in the normal myocardium than in the hypertrophied myocardium. The results suggest that catecholamine-induced cardiac hypertrophy damages the membrane-bound Na+,K(+)-ATPase and causes a cAMP-independent intracellular Ca overload and TDs, thereby permitting abnormal impulse formation, which predisposes the diseased myocardium to develop arrhythmias.

Topics: Action Potentials; Animals; Body Weight; Cardiomegaly; Colforsin; Electric Stimulation; Heart; Isoproterenol; Male; Organ Size; Rats; Rats, Inbred Strains; Ryanodine; Sodium-Potassium-Exchanging ATPase

Newborn rats were rendered hyperthyroid (daily subcutaneous injections of L-triiodothyronine, 10 micrograms 100 g-1 body weight) or hypothyroid (0.05% 6-n-propyl-2-thiouracil in drinking water to nursing mothers) during the first 3 weeks of postnatal life. Compared with the euthyroid group, hyperthyroidism resulted in: (1) cardiac enlargement with right ventricular preponderance, (2) increased cardiac contractile function, (3) increased Ca2+ uptake by the sarcoplasmic reticulum (SR), (4) decreased sensitivity to the negative inotropic effect of verapamil and (5) greater inhibition of contractile function by ryanodine. Hypothyroidism generally resulted in opposite changes. The data suggest that the development of the heart and its contractile function during early postnatal life depends on the plasma level of thyroid hormones. In particular, the relative contribution of the SR and sarcolemmal Ca2+ transport to the control of cardiac contractility seems to be markedly affected by altered thyroid states. The postnatal maturation of the SR function is accelerated in hyperthyroidism but retarded in hypothyroidism. Consequently, hyperthyroid hearts appear to be less dependent and hypothyroid ones more dependent on trans-sarcolemmal Ca2+ fluxes when compared with age-matched euthyroid animals.

Topics: Animals; Animals, Newborn; Body Weight; Calcium; Male; Myocardial Contraction; Myocardium; Rats; Rats, Inbred Strains; Ryanodine; Sarcoplasmic Reticulum; Thyroid Gland; Thyroid Hormones; Verapamil

Differences in caffeine-induced contraction in smooth muscle of resistance vessels from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar Kyoto rats (WKY) were investigated by using mesenteric artery preparations. The contraction induced by caffeine (10 mM) was greater in SHRSP preparations, both in the presence and absence of Ca (10 min after Ca removal). Caffeine-induced contraction was gradually decreased by the removal of extracellular Ca. No significant difference was observed in the time course of the decay of the contraction between SHRSP and WKY preparations, and the contraction disappeared when the time in Ca-free solution exceeded 80 min. The contraction induced by high-K-Tyrode's solution was completely abolished within 10 min after Ca removal, both in SHRSP and WKY preparations. Caffeine-induced contraction could be blocked by procaine or ryanodine. The results suggest that caffeine induces contraction by releasing Ca from sarcoplasmic reticulum, and that the release of Ca is greater in SHRSP vascular smooth muscle. It is also suggested that sarcoplasmic reticulum is leaky for stored Ca when extracellular Ca is removed, and that the rate of leakage does not differ between smooth muscle cells of SHRSP and WKY mesenteric arteries.

Topics: Animals; Blood Pressure; Body Weight; Caffeine; Calcium; Cerebrovascular Disorders; Dose-Response Relationship, Drug; In Vitro Techniques; Mesenteric Arteries; Muscle Contraction; Muscle, Smooth, Vascular; Potassium; Procaine; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Ryanodine