Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0038454 (stroke)
147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In muscle fibres labelled with iodoacetamidotetramethylrhodamine at Cys707 of the myosin heavy chain, the probes have been reported to change orientation when the fibre is activated, relaxed or put into rigor. In order to test whether these motions are indications of the cross-bridge power stroke, we monitored tension and linear dichroism of the probes in single glycerol-extracted fibres of rabbit psoas muscle during mechanical transients initiated by laser pulse photolysis of caged ATP and caged ADP. In rigor dichroism is negative, indicating average probe absorption dipole moments oriented more than 54.7 degrees away from the fibre axis. During activation from rigor induced by photoliberation of ATP from caged ATP in the presence of calcium, the dichroism reversed sign promptly (half-time 12.5 ms for 500 microM-ATP) upon release of ATP, but then changed only slightly during tension development 20 to 100 milliseconds later. During the onset of rigor following transfer of the fibre from an ATP-containing relaxing solution to a rigor medium lacking ATP, force generation preceded the change in dichroism. The dichroism change occurred slowly (half-time 47 s), because binding of ADP to sites within the muscle fibre limited its rate of diffusion out of the fibre. When ADP was introduced or removed, the dichroism transient was similar in time course and magnitude to that obtained after the introduction or removal of ATP. Neither adding nor removing ADP produced substantial changes in force. These results demonstrate that orientation of the rhodamine probes on the myosin head reflects mainly structural changes linked to nucleotide binding and release, rather than rotation of the cross-bridge during force generation.
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PMID:Transients in orientation of a fluorescent cross-bridge probe following photolysis of caged nucleotides in skeletal muscle fibres. 153 Sep 78

Cold exposure (6 weeks at 4 degrees C) of normotensive (Wistar-Kyoto) and stroke-prone spontaneously hypertensive female rats led to cardiac hypertrophy (in stroke-prone spontaneously hypertensive rats), increased the level of plasma thyroxine, and increased the alpha-myosin heavy chain expression in the left ventricle. In contrast, myosin heavy chain expression of both main mesenteric artery and uterus was not affected by cold stress and chronic hypertension, suggesting different regulation of myosin heavy chain expression in smooth and cardiac muscle in vivo.
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PMID:The influence of cold stress on the myosin heavy chain expression of cardiac and smooth muscle in normotensive and spontaneously hypertensive female rats. 183 32

Stroke-prone spontaneously hypertensive rats were used for our investigation of the influence of prepubertal gonadectomy and testosterone substitution on blood pressure, cardiac hypertrophy, and the expression of ventricular myosin heavy chain (MHC) isoenzymes at different developmental stages. Blood pressure and the degree of cardiac hypertrophy were decreased by castration and increased by testosterone substitution. We found the same relative distributions of MHC isoforms on the protein level (investigated by pyrophosphate electrophoresis) and on the messenger RNA level (investigated by the polymerase chain reaction). Castration favored the expression of the beta-MHC form, and testosterone substitution enhanced the expression of the alpha-MHC form. These effects were more pronounced in 8-week-old than in 14-16-week-old animals. We conclude that testosterone regulates cardiac MHC expression on a pretranslational level. This regulation is independent of hemodynamic load or cardiac hypertrophy.
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PMID:Regulation of myosin heavy chain expression in the hearts of hypertensive rats by testosterone. 214 May 38

Latissimus dorsi (LD) muscles of six canines were studied to assess changes induced by electrical conditioning and to quantify the capacity of these muscles to perform hemodynamic work. Muscles were conditioned using burst stimuli delivered over an 8-wk period. Contralateral LD were used as control. Muscles were tested in situ to simulate anticipated linear-pull cardiac assist conditions. This training process reduced muscle mass and cross-sectional area by 16 and 17%, respectively. Muscle phenotype shifted to a predominantly "slow" form by coordinate reduction of myosin heavy chain (MHC) 2A expression and increased expression of the MHC beta/slow form. Force generation was reduced by 54%, and contractile duration increased 13%. Fatigue resistance was markedly enhanced, and chronic stroke work increased from 0.19 to 0.72 mJ/g. The highest steady-state power output (2.06 mW/g) was obtained from one muscle fully converted to a slow phenotype. These data suggest that single LD trained via conventional techniques can provide energy sufficient for partial cardiac assistance but cannot sustain work levels needed to achieve total circulatory support.
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PMID:Functional properties of conditioned skeletal muscle: implications for muscle-powered cardiac assist. 927 56

Myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) had decreased Na+/Ca2+ exchange currents (I Na/Ca; 3 Na+ out:1 Ca2+ in) and sarcoplasmic reticulum (SR)-releasable Ca2+ contents. These defects in Ca2+ regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardial Ca2+ regulation, the present study examined whether 6-8 wk of high-intensity sprint training (HIST) would ameliorate some of the cellular maladaptations observed in post-MI rats with limited exercise activity (Sed). In MI rats, HIST did not affect citrate synthase activities of plantaris muscles but significantly increased the percentage of cardiac alpha-myosin heavy chain (MHC) isoforms (57.2 +/- 1.9 vs. 49.3 +/- 3.5 in MI-HIST vs. MI-Sed, respectively; P < or = 0.05). At the single myocyte level, HIST attenuated cellular hypertrophy observed post-MI, as evidenced by reductions in cell lengths (112 +/- 4 vs. 130 +/- 5 micrograms in MI-HIST vs. MI-Sed, respectively; P < or = 0.005) and cell capacitances (212 +/- 8 vs. 242 +/- 9 pF in MI-HIST vs. MI-Sed, respectively; P < or = 0.015). Reverse I Na/Ca was significantly lower (P < or = 0.0001) in myocytes from MI-Sed rats compared with those from rats that were sham operated and sedentary. HIST significantly increased reverse I Na/Ca (P < or = 0.05) without affecting the amount of Na+/Ca2+ exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca2+ content, as estimated by integrating forward I Na/Ca during caffeine-induced SR Ca2+ release, was also significantly increased (P < or = 0.02) by HIST in MI myocytes. We conclude that the enhanced cardiac output and stroke volume in post-MI rats subjected to HIST are mediated, at least in part, by reversal of cellular maladaptations post-MI.
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PMID:Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes. 947 64

In elderly patients, aortic stiffness is a major determinant of increased end-systolic stress leading to left ventricular (LV) hypertrophy with impaired cardiac performance. However, in a rat model of aortic elastocalcinosis (induced by vitamin D(3)-nicotine [VDN] treatment), brief exposure (1 month) to increased aortic stiffness modified neither cardiac function nor cardiac structure. Here we report the impact of longer exposure (3 months) to aortic stiffness. Three months after induction of aortic stiffness, aortic characteristic impedance was measured in awake rats, 8 control and 10 VDN. Stroke volume was measured (electromagnetic probe) at baseline and after acute volume overload. LV weight/body weight ratio, collagen, and myosin heavy chain (MHC) contents were determined. Although aortic characteristic impedance increased (controls, 32+/-2; VDN rats, 50+/-8 10(3) dyne. s/cm(5); P=0.0248), stroke volume was maintained in VDN rats at baseline (controls, 223+/-18; VDN, 211+/-13 microL) and after volume overload (controls, 378+/-14; VDN, 338+/-15 microL). However, LV weight/body weight ratio (controls, 1.54+/-0.07; VDN, 1.73+/-0.05 g/kg; P=0.0397) and LV collagen content (controls, 31+/-4; VDN, 52+/-4 microgram/g dry wt; P=0.0192) increased. A shift from alpha-MHC (controls, 82+/-2%; VDN, 69+/-3%; P=0.0056) to beta-MHC (controls, 18+/-2%; VDN, 31+/-3%; P=0. 0056) was also observed. Three months' exposure to increased aortic stiffness in VDN rats induced LV hypertrophy with moderate interstitial fibrosis and a shift in the MHC-isoform pattern. Such structural adaptation maintains LV performance.
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PMID:Cardiac consequences of prolonged exposure to an isolated increase in aortic stiffness. 1040 25

Angiotensin-converting enzyme inhibitors (ACEIs) cause regression of hypertensive left ventricular hypertrophy (LVH) by reducing angiotensin II, increasing bradykinin, or both. The mechanisms of these cardioprotective effects remain controversial. The aims of this study were to determine whether the cardioprotective effects of ACEIs are mediated by reducing angiotensin II and whether ACEIs ameliorate the morphologic, physiologic, and biochemical changes in the hearts of stroke-prone spontaneously hypertensive rats (SHRSPs). Male SHRSPs were treated with hydralazine, captopril, or candesartan, an angiotensin II type 1 receptor (AT1R) antagonist, from age 12 to 24 weeks. We measured systolic blood pressure (SBP), left ventricular weight (LVW), left ventricular (LV) myocyte cross-sectional area (myocyte size), LV Interstitial collagen volume fraction (ICVF), perivascular collagen area/luminal area ratio (PVCA/LA), the medial area to luminal area ratio (MA/LA), the relative amount of V3 myosin heavy chain (MHCV3), and coronary reserve maximum (coronary flow max/ventricular weight (CFmax/VW)). These parameters were compared with those of untreated SHRSPs and Wistar-Kyoto rats (WKYs). SHRSPs exhibited decreased coronary reserve and LVH with an increase in myocyte size, PVCA/LA, MA/LA, and MHCV3 at 12 weeks of age. In addition to these changes, 24-week-old SHRSPs showed an increase in ICVF. The LVW, coronary reserve, myocyte size, PVCA/LA, ICVF, and MHCV3 of SHRSPs treated with captopril or candesartan all approached control values. In contrast, hydralazine decreased only ICVF. These results suggest that ACEIs regress LVH and normalize coronary reserve by modulating the effects of angiotensin II via AT1R on the induction of cardiomyocyte hypertrophy, perivascular fibrosis, and medial thickening of intramyocardial coronary arteries in SHRSPs. We concluded that these effects, in addition to the reduction of SBP, are important in causing the regression of LVH.
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PMID:Angiotensin II-induced cardiomyocyte hypertrophy and cardiac fibrosis in stroke-prone spontaneously hypertensive rats. 1077 52

We recently evaluated treadmill aerobic running capacity in 11 inbred strains of rats and found that isolated working left ventricular function correlated (r = 0.86) with aerobic running capacity. Among these 11 strains the Buffalo (BUF) hearts produced the lowest and the DA hearts the highest isolated cardiac output. The goal of this study was to investigate the components of cardiac function (i.e., coronary flow, heart rates, stroke volume, contractile dynamics, and cross-bridge cycling) to characterize further the BUF and DA inbred strains as potential models of contrasting myocardial performance. Cardiac performance was assessed using the Langendorff-Neely working heart preparation. Isolated DA hearts were superior (P < 0.05) to the BUF hearts for cardiac output (63%), stroke volume (60%), aortic +dP/dt (47%), and aortic -dP/dt (46%). The mean alpha/beta-myosin heavy chain (MHC) isoform ratio for DA hearts was 21-fold higher relative to BUF hearts. At the steady-state mRNA level, DA hearts had a fivefold higher alpha/beta-ratio than the BUF hearts. The mean rate of ATP hydrolysis by MHCs was 64% greater in DA compared with BUF ventricles. These data demonstrate that the BUF and DA strains can serve as genetic models of contrasting low and high cardiac function.
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PMID:Myocardial function in rat genetic models of low and high aerobic running capacity. 1183 92

The potential to explore myosin function through the alternative exons and mutations of the single muscle myosin heavy chain gene, Mhc of Drosophila requires detailed kinetic analysis of the myosins. We have obtained microgram quantities of enzymatically active Drosophila myosin and subfragment 1 (S1) from dissected indirect flight muscles. Using recent developments in stopped-flow and flash-photolysis methods combined with fluorescent/light scattering technologies we have determined some of the key kinetic parameters of actin-myosin and myosin-nucleotide interactions. The rate of ATP-induced dissociation of actin from Drosophila myosin (0.23 microM(-1) s(-1)) and subfragment 1 (S1, 0.82 microM(-1) s(-1)) are both fast and similar to values measured for mammalian skeletal muscle myosins and S1 fragments respectively. The ATP-induced cross bridge dissociation of Drosophila acto.S1 is expected to be fast since, for a rapidly contracting muscle like the Drosophila flight muscle, the post power stroke cross bridge must detach rapidly from actin or become a drag on the contracting filament. ATP-induced detachment is preceded by ADP release and this is proposed as the rate-limiting step that defines muscle shortening velocity. We show that the affinity of ADP for acto.S1 at 400 microM is 2-3 fold weaker than fast vertebrate myosins. This leads to an estimate of the ADP release rate constant of 4000 s(-1). We show that this predicts a maximum shortening velocity very similar to that obtained from in vivo estimates of indirect flight muscle shortening. The data is therefore compatible with ADP dissociation limiting the in vivo shortening velocity.
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PMID:Isolation and kinetic characterisation of myosin and myosin S1 from the Drosophila indirect flight muscles. 1487 Sep 64

The disability of patients after stroke is generally attributed to upper motor neuron defects, but secondary changes in paretic muscle may enhance the disability. We analyzed the molecular phenotype and metabolic profile of the paretic and nonparetic vastus lateralis (VL) and we measured the severity of gait deficit in 13 patients at least 6 months after ischemic stroke. The results showed a significant increase in the proportion of fast myosin heavy chain (MHC, 68 +/- 14%) in the paretic compared to the nonparetic VL (50 +/- 13%). The specific activity of citrate synthase and glyceraldehyde phosphodehydrogenase was not significantly different between the two sides. The proportion of fast MHC was inversely associated with severity of gait deficit indexed by self-selected walking speed in the paretic leg, but not the nonparetic leg. Our findings demonstrate significant and potentially modifiable secondary biologic changes in hemiparetic muscle phenotype that may contribute to the disability of stroke.
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PMID:Muscle molecular phenotype after stroke is associated with gait speed. 1526 37


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