Biomedical subjects

P Thorén

Publications and source records attributed to P Thorén.

At least 19 recordsLinked to original sources

PubMed2006

SYBR Green real-time reverse transcription-polymerase chain reaction assay for the generic detection of coronaviruses.

Coronaviruses are etiologic agents of respiratory and enteric diseases in humans and in animals. In this study, a one-step real-time reverse transcription-polymerase chain reaction (RT-PCR) assay based on SYBR Green chemistry and degenerate primers was developed for the generic detection of coronaviruses. The primers, designed in the open reading frame 1b, enabled the detection of 32 animal coronaviruses including strains of canine coronavirus, feline coronavirus, transmissible gastroenteritis virus (TGEV), bovine coronavirus (BCoV), murine hepatitis virus (MHV) and infectious bronchitis virus (IBV). A specific amplification was also observed with the human coronaviruses (HCoV) HCoV-NL63, HCoV-OC43, HCoV-229E and severe acute respiratory syndrome coronavirus (SARS-CoV). The real-time RT-PCR detected down to 10 cRNA copies from TGEV, BCoV, SARS-CoV and IBV. In addition, the assay exhibited a high sensitivity and specificity on clinical samples from different animal species. The developed assay represents a potential tool for laboratory diagnostics and for detecting still uncharacterized coronaviruses.

Animals↗

PubMed2006

Development of a real-time PCR assay based on primer-probe energy transfer for the detection of swine vesicular disease virus.

A real-time PCR assay based on primer-probe energy transfer (PriProET) was developed to detect swine vesicular disease virus (SVDV). Specificity tests of SVDV and heterologous virus showed specific amplification of SVDV strains only. The amplification plot for the closely related Coxsackievirus B5 remained negative. The sensitivity of assay was five copies of viral genome equivalents. A key point of the assay is tolerance toward mutations in the probe region. Melting curve analysis directly after PCR, with determination of probe melting point, confirmed specific hybridisation of the SVDV strains. Eight of twenty SVDV strains tested, revealed shifted melting points that indicated mutations in the probe region. All predicted mutations were confirmed by nucleotide sequencing. With the PriProET system there is a chance to identify phylogenetically divergent strains of SVDV, which may appear negative in other probe-based real-time PCR assays. At the same time, any difference in melting points may provide an indication of divergence in the probe region. The high sensitivity, specificity, and tolerance toward mutations in the probe region of the SVDV PriProET assay may improve the early and rapid detection of a wide range of SVDV strains, allowing reduced turnaround time and the use of high-throughput, automated technology.

Animals↗

PubMed2005

Electrocardiographic characterization of stress-induced myocardial infarction in atherosclerotic mice.

AIM: We have previously shown that mental and hypoxic stress can trigger the development of myocardial infarction (MI) in atherosclerotic apoE(-/-) x LDLR(-/-) mice. The purpose of the present study was to characterize the interval between stress and MI and determine whether electrophysiological changes precede the precipitation of an infarct by assessing telemetry recordings of the electrocardiogram. METHODS: Isoflurane anaesthetized apoE(-/-) x LDLR(-/-) (n = 16) and C57BL/6J (n = 8) mice were exposed to systemic hypoxia by reducing the inhaled oxygen concentration to 10% for 10 min. Mental stress was induced in eight conscious apoE(-/-) x LDLR(-/-) and eight C57BL/6J mice by blowing air into the cage. Physiological parameters were recorded every 30 min for 2-6 days by implanted transmitters. RESULTS: During stress all mice developed transient ischaemic STU-area changes, which returned to normal at the end of stress. During the recovery phase (6 days) 50% (4/8) of the mentally stressed apoE(-/-) x LDLR(-/-) mice developed increased STU-area variability (P < 0.05) followed by dramatic STU-area elevations and spontaneous death at approximately 12-24 h. In hypoxia-exposed apoE(-/-) x LDLR(-/-) mice 56% (9/16) developed MI as determined by elevated serum levels of the infarction marker troponin T which correlated with increased variability in the STU-area (P < 0.05). CONCLUSION: This is the first mouse model showing that increased STU-area variability is indicative of MI development in atherosclerotic mice following ischaemic stress. Furthermore, our findings suggest a two-phase pathway for the infarction development: an initial phase comprising a transient ischaemic response which triggers a delayed second phase of ischaemia and MI.

Animals↗

PubMed2003

Experimental infection of cows with bovine viral diarrhoea virus in early pregnancy - findings in serum and foetal fluids.

Nineteen pregnant cows were experimentally infected with bovine viral diarrhoea virus (BVDV) between day 74 and 81 of pregnancy. All cows became infected and developed serum antibodies. Sixteen of the cows delivered persistently infected (PI) offspring, whereas the remaining three gave birth to calves with detectable serum antibodies and free from BVDV. The 16 cows with PI foetuses developed higher levels of antibodies in serum during pregnancy than did their three peers carrying non-PI calves. Multivariate analysis showed that the antibody levels in these two groups of cows were significantly different from day 135 of pregnancy. Foetal fluid was successfully collected from 18 of the 19 infected cows and from five uninfected control cows between 10 and 24 days before delivery by use of a percutaneous, blind puncture technique. No negative effects were observed in the cows or their offspring. BVDV was isolated and detected with an immunoperoxidase test in foetal fluid from 13 of the 16 cows carrying PI foetuses, and from 15 of the cows when a quantitative fluorescent polymerase chain reaction (PCR) technique was used. The negative sample in the PCR assay was positive for BVDV antibodies. The number of viral copies per microlitre in foetal fluids varied between 103 and 1080 in the positive samples. All samples taken from the cows carrying non-PI foetuses were negative for BVDV in both assays. In this experiment, examination of either serum or foetal fluids could identify the cows carrying a PI foetus. Examination of serum for BVDV antibodies was a reliable indicator of a PI foetus if the serum was collected during the last 2 months of pregnancy. For examination of foetal fluids, both viral and serological analyses should be performed. For viral analysis, PCR should be the test of choice. High levels of BVDV antibodies in conjunction with a negative result in the PCR may be indicative of a false-negative virus result. Further experience with the method of collection of foetal fluids is necessary for evaluation of its safety. Investigation of pregnant cows in order to discover a PI offspring before it is born could be a useful tool in control and eradication of BVDV.

Animals↗

PubMed2002

Cyclic fluctuations in the cardiac performance of the isolated Langendorff-perfused mouse heart: pyruvate abolishes the fluctuations and has an anti-ischaemic effect.

During the development of a Langendorff preparation of isolated mouse hearts, hitherto undescribed cyclic fluctuations in left ventricular pressure and coronary flow were independently observed in three laboratories. Isolated mouse hearts were perfused with crystalloid glucose-containing Krebs-Hensleit buffer in a constant pressure model, and left ventricular pressures were measured via an intraventricular balloon catheter. After acquiring technical skill in preparing the mouse hearts, the perfusionists observed that fluctuations in cardiac performance with a cycle period lasting 5-10 min occurred shortly after initiation of perfusion. Each fluctuation cycle consisted of a phase of increase and a phase of decrease. Synchronized with the fluctuations in left ventricular pressure, increases and decreases in dP/dt max took place. Analogous fluctuations in coronary flow occurred, with onset 1-2 min later than changes in left ventricular systolic pressure. In some preparations a gradual ST-segment elevation was seen on the electrocardiogram during the systolic pressure increase phase. The amplitude of the fluctuations could be augmented by increasing the perfusion pressure, and reduced, but not abolished, by lowering the pressure. Changes in buffer calcium, magnesium, or sodium concentration did not alter the fluctuations, nor did any change of anaesthetics, mouse strain, or left ventricular drainage. Altering the perfusion mode from constant pressure to constant flow did not prevent the occurrence of the cyclic fluctuations. The hearts became stable and the fluctuations disappeared when the buffer was supplemented with 2 mm pyruvate. In the present study, pyruvate given throughout stabilization and reperfusion also markedly attenuated the ischaemic insult, as evidenced by the delayed ischaemic contracture and a reduced magnitude of ischaemic contracture. A cardioprotective effect was only visible at early reperfusion, did not affect the final functional recovery. In conclusion, a phenomenon of cyclic fluctuations in left ventricular pressure followed by fluctuations in coronary flow was observed in isolated mouse hearts. These could be abolished by adding 2 mm pyruvate to the perfusion buffer. Pyruvate in the buffer also markedly attenuated the post-ischaemic deterioration of cardiac performance seen in this mouse model.

Animals↗

PubMed2001

Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect.

BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.

Animals↗

PubMed2001

Contraction and intracellular Ca(2+) handling in isolated skeletal muscle of rats with congestive heart failure.

A decreased exercise tolerance is a common symptom in patients with congestive heart failure (CHF). This decrease has been suggested to be partly due to altered skeletal muscle function. Therefore, we have studied contractile function and cytoplasmic free Ca(2+) concentration ([Ca(2+)](i), measured with the fluorescent dye indo 1) in isolated muscles from rats in which CHF was induced by ligation of the left coronary artery. The results show no major changes of the contractile function and [Ca(2+)](i) handling in unfatigued intact fast-twitch fibers isolated from flexor digitorum brevis muscles of CHF rats, but these fibers were markedly more susceptible to damage during microdissection. Furthermore, CHF fibers displayed a marked increase of baseline [Ca(2+)](i) during fatigue. Isolated slow-twitch soleus muscles of CHF rats displayed slower twitch contraction and tetanic relaxation than did muscles from sham-operated rats; the slowing of relaxation became more pronounced during fatigue in CHF muscles. Immunoblot analyses of sarcoplasmic reticulum proteins and sarcolemma Na(+),K(+)-ATPase showed no difference in flexor digitorum brevis muscles of sham-operated versus CHF rats. In conclusion, functional impairments can be observed in limb muscle isolated from rats with CHF. These impairments seem to mainly involve structures surrounding the muscle cells and sarcoplasmic reticulum Ca(2+) pumps, the dysfunction of which becomes obvious during fatigue.

Animals↗

PubMed2001

Reduced antinociception and plasma extravasation in mice lacking a neuropeptide Y receptor.

Neuropeptide Y (NPY) is believed to exert antinociceptive actions by inhibiting the release of substance P and other 'pain neurotransmitters' in the spinal cord dorsal horn. However, the physiological significance and potential therapeutic value of NPY remain obscure. It is also unclear which receptor subtype(s) are involved. To identify a possible physiological role for the NPY Y1 receptor in pain transmission, we generated NPY Y1 receptor null mutant (Y1-/-) mice by homologous recombination techniques. Here we show that Y1-/- mice develop hyperalgesia to acute thermal, cutaneous and visceral chemical pain, and exhibit mechanical hypersensitivity. Neuropathic pain is increased, and the mice show a complete absence of the pharmacological analgesic effects of NPY. In the periphery, Y1 receptor activation is sufficient and required for substance P release and the subsequent development of neurogenic inflammation and plasma leakage. We conclude that the Y1 receptor is required for central physiological and pharmacological NPY-induced analgesia and that its activation is both sufficient and required for the release of substance P and initiation of neurogenic inflammation.

Animals↗

PubMed2001

Activation of inducible nitric oxide synthase/nitric oxide by curli fibers leads to a fall in blood pressure during systemic Escherichia coli infection in mice.

Septic shock, a major cause of death, is characterized by a pathophysiologic increased production of nitric oxide (NO), which leads to vasodilation and myocardial toxicity. Septic Escherichia coli frequently express proteinaceous curli fibers. In this study, curliated E. coli induced high levels of NO by directly inducing type 2 nitric oxide synthase (NOS2) both in vitro and in vivo. More severe hypotension and higher plasma nitrite/nitrate levels were seen in wild type mice systemically infected with curliated E. coli than in animals infected with E. coli mutants that lacked curli proteins. Blood pressure remained stable in NOS2-deficient mice with curliated bacteria. Increased heart rates, transient hypothermia, and loss of gross activity were seen in all mice, regardless of curli expression. Study results suggest that expression of curli fibers by E. coli activates the NO/NOS2 arm of the innate immune system, which leads to a significant fall in blood pressure.

Animals↗

PubMed2001

Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice.

Thyroid hormone governs a diverse repertoire of physiological functions through receptors encoded in the receptor genes alpha and beta, which each generate variant proteins. In mammals, the alpha gene generates, in addition to the normal receptor TRalpha1, a non-hormone-binding variant TRalpha2 whose exact function is unclear. Here, we present the phenotype associated with the targeted ablation of TRalpha2 expression. Selective ablation of TRalpha2 resulted in an inevitable, concomitant overexpression of TRalpha1. Both TRalpha2 +/- and -/- mice show a complex phenotype with low levels of free T3 and free T4, and have inappropriately normal levels of TSH. The thyroid glands exhibit mild morphological signs of dysfunction and respond poorly to TSH, suggesting that the genetic changes affect the ability of the gland to release thyroid hormones. However, the phenotype of the mutant mice also has features of hyperthyroidism, including decreased body weight, elevated heart rate, and a raised body temperature. Furthermore, TRalpha2-/- and TRalpha2+/- mice are obese and exhibit skeletal alterations, associated with a late-onset growth retardation. The results thus suggest that the overexpression of TRalpha1 and the concomitant decrease in TRalpha2 expression lead to a mixed hyper- and hypothyroid phenotype, dependent on the tissue studied. The phenotypes suggest that the balance of TRalpha1:TRalpha2 expressed from the TRalpha gene provides an additional level of tuning the control of growth and homeostasis in mammalian species.

Animals↗

PubMed2001

Molecular diagnosis of animal diseases: some experiences over the past decade.

The experiences of a veterinary research and diagnostic laboratory are summarized on the development and application of the PCR to diagnose a wide range of viral diseases in animals. The group started the routine diagnostic application of the PCR as early as 1988 and today a total of 35 nested PCR assays are in routine use for the detection of 15 DNA and 20 RNA viruses. Special tools and laboratory practice were applied to avoid false-positive results, while false-negatives are avoided by internal controls (mimics). At present, the classical nested PCR methods are being replaced by real-time TaqMan and molecular beacon assays and the multiplex real-time PCR detection of viruses is also under development. By direct sequencing of the PCR products, phylogeny studies are performed and molecular epizootiology results are provided for rapid and exact identification of virus variants. Molecular epizootiology also contributes to trace the routes of virus spreading on large geographic areas. Recently, large efforts have been made to follow the recommendations of Office International des Epizooties for the standardization and international harmonization of the molecular diagnostic assays.

Animal Diseases↗

PubMed2000

Enhancement of natural immunity seen after voluntary exercise in rats. Role of central opioid receptors.

Chronic voluntary exercise in wheels for 5 weeks in spontaneously hypertensive rats (SHR) augments in vivo natural killer (NK) cell cytotoxicity. Endogenous beta-endorphin is increased in cerebrospinal fluid after voluntary exercise in rats and we have recently shown that beta-endorphin administered i.c.v. augments NK cell mediated cytotoxicity in vivo in a similar way as chronic voluntary exercise. We have now further investigated the involvement of central opioid systems in the exercise-induced augmentation in natural immunity. Exercise consisted of voluntary running in wheels for 5 weeks. In vivo cytotoxicity was measured as clearance of injected 51Cr-labeled YAC-1 lymphoma cells from the lungs. The clearance of YAC-1 cells in vivo was significantly increased in runners as compared to sedentary controls. Selective delta, kappa, or mu-opioid receptor antagonists were administered i.c.v. with osmotic minipumps during the last 6 days of the 5 weeks of running. The delta-receptor antagonist naltrindole (40-50 microg/day) significantly but not completely inhibited the enhanced NK-cell cytotoxicity seen after 5 weeks of exercise. Neither the kappa-receptor antagonist nor-BNI or the mu-receptor antagonist beta-FNA influenced the augmentation in NK cell cytotoxicity. Nor-BNI per se significantly augments in vivo cytotoxicity, indicating some inhibiting effect on natural immunity that could be mediated through the kappa-opioid receptor. Our data suggest the involvement of central delta-opioid receptors in the enhancement of natural cytotoxicity seen after chronic voluntary exercise.

Animals↗

PubMed2000

Endothelial dysfunction in atherosclerotic mice: improved relaxation by combined supplementation with L-arginine-tetrahydrobiopterin and enhanced vasoconstriction by endothelin.

1. Mice lacking the apolipoprotein E and low density lipoprotein receptor genes (E degrees xLDLR degrees ) develop atherosclerosis and endothelial dysfunction. The aim of this study was to characterize the roles of L-arginine and tetrahydrobiopterin (BH(4)) for endothelium-dependent relaxation and the changes in the vasoconstrictor response to endothelin-1 (ET-1) in thoracic aortic rings of E degrees xLDLR degrees mice. 2. Histological examination revealed severe atherosclerosis of the thoracic aorta of E degrees xLDLR degrees mice. Relaxations induced by acetylcholine (Ach), but not that to sodium nitroprusside, were significantly impaired in E degrees xLDLR degrees mice compared to control mice indicating attenuated endothelium-dependent relaxations. 3. Preincubation with the nitric oxide (NO) substrate L-arginine did not affect, whereas the co-factor for NO synthase, BH(4), slightly improved the relaxations induced by Ach. Combined preincubation with L-arginine and BH(4) induced a pronounced enhancement of Ach-induced relaxations in E degrees xLDLR degrees mice. The relaxations induced by Ach in E degrees xLDLR degrees mice in the presence of L-arginine and BH(4) were not different from those observed in control mice. 4. Preincubation with superoxide dismutase did not affect Ach-induced relaxations in aorta from E degrees xLDLR degrees mice. 5. The contractile response to ET-1 was enhanced in E degrees xLDLR degrees mouse aorta. The contractions were abolished by the ET(A) receptor antagonist LU 135252. The ET(B) receptor agonist sarafotoxin 6c did not induce contractions or relaxations. 6. It is concluded that endothelial dysfunction of E degrees xLDLR degrees mouse aorta is reversed by combined administration of L-arginine and BH(4). In addition, the ET(A) receptor-mediated vasoconstriction by ET-1 is enhanced in E degrees xLDLR degrees mice.

Acetylcholine↗

PubMed2000

Running and cocaine both upregulate dynorphin mRNA in medial caudate putamen.

Physical activities such as long-distance running can be habit forming and associated with a sense of well-being to a degree that justifies comparison with drug-induced addictive behaviours. To understand molecular similarities and dissimilarities controlling these behaviours in humans we compared the effects of running in running wheels to the effects of chronic cocaine or morphine administration on mRNA levels in brain reward pathways in the inbred Fischer and Lewis rat strains. These strains are both inbred from the Sprague-Dawley strain; Lewis rats display a higher preference towards addictive drugs and running than do Fischer rats. After chronic cocaine or running a similar increase of dynorphin mRNA in medial caudate putamen was found in the Lewis rat, suggesting common neuronal adaptations in this brain region to both cocaine and running. Fischer and Lewis rats both responded to cocaine with increased dynorphin mRNA levels in medial caudate putamen. However, only Lewis rats increased dynorphin mRNA after running, possibly reflecting the much higher degree of running by the Lewis strain as compared to the Fischer strain. Moreover, the running-induced upregulation of dynorphin mRNA was blocked by the opioid receptor antagonist naloxone. We suggest that running increases dynorphin mRNA by a mechanism that involves endogenous opioids. The voluntary wheel-running model in rats might be used to study natural reward and compulsive behaviours and possibly also to screen candidate drugs for treatment of compulsive disorders.

Analgesics, Opioid↗

PubMed2000

Isometric force and endurance in soleus muscle of thyroid hormone receptor-alpha(1)- or -beta-deficient mice.

The specific role of each subtype of thyroid hormone receptor (TR) on skeletal muscle function is unclear. We have therefore studied kinetics of isometric twitches and tetani as well as fatigue resistance in isolated soleus muscles of R-alpha(1)- or -beta-deficient mice. The results show 20-40% longer contraction and relaxation times of twitches and tetani in soleus muscles from TR-alpha(1)-deficient mice compared with their wild-type controls. TR-beta-deficient mice, which have high thyroid hormone levels, were less fatigue resistant than their wild-type controls, but contraction and relaxation times were not different. Western blot analyses showed a reduced concentration of the fast-type sarcoplasmic reticulum Ca(2+)-ATPase (SERCa1) in TR-alpha(1)-deficient mice, but no changes were observed in TR-beta-deficient mice compared with their respective controls. We conclude that in skeletal muscle, both TR-alpha(1) and TR-beta are required to get a normal thyroid hormone response.

Animals↗

PubMed1999

Somatic nerve stimulation and cholera-induced net fluid secretion in the small intestine of the rat: evidence for an opioid effect.

The effects of somatic nerve stimulation on cholera toxin induced secretion was investigated in vivo in anaesthetised rats. Small intestinal secretion was induced with cholera toxin and measured by a gravimetric technique. Afferent stimulation (pulse frequency within train; 100 Hz; train duration: 50 ms; train frequency: 3 Hz) of the sciatic nerve over 30 min significantly reduced the net fluid secretion both during (P < 0.05) and after cessation of the stimulation (P < 0.01). The greatest effect was obtained immediately after the termination of the nerve stimulation when the secretion was reversed to net fluid absorption. The opioid receptor antagonist naloxone (10 mg kg(-1) i.v.) administrated during the stimulation, significantly inhibited the antisecretory effect seen after the stimulation, thus no significant difference was seen between the control period and the periods after cessation of the stimulation. The opioid receptor antagonist naloxone methiodide (10 mg kg(-1) i.v.), which does not cross the blood-brain barrier, partly inhibited the antisecretory effects but not with the same magnitude as naloxone, thus the net fluid secretion was still significantly inhibited after the stimulation (P < 0.05). We conclude that afferent stimulation of the sciatic nerve strongly inhibits the cholera toxin induced secretion in the small intestine. This inhibition involves primarily a central opioid mechanism and to a lesser extent peripheral opioid mechanism.

Acupuncture Therapy↗

PubMed1999

Addiction-prone Lewis but not Fischer rats develop compulsive running that coincides with downregulation of nerve growth factor inducible-B and neuron-derived orphan receptor 1.

We have examined the effects of chronic voluntary running for 30 d on the levels of nerve growth factor inducilble-B (NGFI-B) and neuron-derived orphan receptor 1 (NOR1) mRNAs in Fischer and Lewis rats. The aim was to compare the addiction-prone Lewis rat strain to the Fischer strain in a plausible model for natural reward. The Lewis strain ran markedly more than the Fischer strain, as indicated by the length of running per day when given free access to running wheels. Both strains progressively increased their amount of daily running. By day 14, Lewis rats had reached a maximal level corresponding to 10 km/d, which slowly decreased to approximately 8 km/d. Fischer rats ran considerably less, averaging approximately 1. 5 km/d by day 30. After 30 d of running, levels of mRNA encoding NGFI-B and Nor1 were decreased in cerebral cortex in Lewis but not Fischer rats. The downregulation of NGFI-B mRNA in Lewis rats could not be attenuated by the opioid receptor antagonist naloxone. Instead, naloxone by itself downregulated NGFI-B in striatum and cerebral cortex in both strains. In contrast, naloxone had no effect on Nor1 mRNA levels, although the running-induced downregulation of Nor1 was, in most cases, attenuated by naloxone. Data from the present study suggest that the same genetic factors contributing to the drug addiction-prone behavior of Lewis rats also control the excessive running behavior and that this coincides with downregulation of transcription factors of the NGFI-B family.

Animals↗

PubMed1999

Myocardial infarction mediated by endothelin receptor signaling in hypercholesterolemic mice.

Myocardial infarction is linked to atherosclerosis, yet the sequence leading from silent coronary atherosclerosis to acute myocardial infarction has remained unclear. Here we show that hypercholesterolemic apolipoprotein E-/- low density lipoprotein receptor-/- mice develop not only coronary atherosclerosis but also myocardial infarction. Exposure of mice to mental stress or hypoxia led to acute ischemia, which, in a large proportion of the mice, was followed by electrocardiographic changes, leakage of troponin T, and loss of dehydrogenase from the myocardium, all indicative of acute myocardial infarction. Apoptotic death of cardiomyocytes was followed by inflammation and fibrosis in the heart. All these pathological changes could be prevented by a blocker of the endothelin type A receptor. Thus, stress elicits myocardial infarction through endothelin receptor signaling in coronary atherosclerosis caused by hypercholesterolemia.

Animals↗