Increasing myocardial contraction and blood pressure in C57BL/6 mice during early postnatal development.

Knowledge of the developmental changes of cardiovascular parameters in the genetic background of a mouse strain is important for understanding phenotypic changes in transgenic or knockout mouse models for heart disease. We studied arterial blood pressure and myocardial contractility in mice of the common background strain C57BL/6, aged 21 days [postnatal day 21 (P21)] to 580 days. Heart rate increased during maturation from 396 beats/min at P21 to 551 beats/min at postnatal day 50 (P50), and mean arterial blood pressure increased in parallel from 86 to 110 mmHg and remained constant afterward.

Induction of atrial fibrillation in mice by rapid transesophageal atrial pacing.

Objective: Atrial fibrillation (AF) as an "indicator arrhythmia" for enhanced atrial vulnerability in mouse hearts has not yet been systematically examined. We therefore evaluated a transesophageal rapid atrial stimulation protocol for the induction of AF in C57Bl/6 mice.

Methods: 40 C57Bl/6 mice (19 female and 21 male; 5.

Estrogenic hormone action in the heart: regulatory network and function.

Cardiovascular diseases are the leading cause of death in the industrialised countries and display significant gender-based differences. Estrogen plays an important role in the pathogenesis of heart disease and is able to modulate the progression of cardiovascular disease. The focus on the beneficial influence of estrogen is gradually shifting from the vascular system to the myocardium.

Activation of estrogen receptor beta is a prerequisite for estrogen-dependent upregulation of nitric oxide synthases in neonatal rat cardiac myocytes.

Physiological effects of estrogen on myocardium are mediated by two intracellular estrogen receptors, ERalpha and ERbeta, that regulate transcription of target genes through binding to specific DNA target sequences. To define the role of ERbeta in the transcriptional activation of both endothelial (eNOS) and inducible nitric oxide synthase (iNOS) in cardiac myocytes, we used the complete ER-specific antagonist R,R-tetrahydrochrysene (R,R-THC). R,R-THC inhibited activation of iNOS/eNOS promoter-luciferase reporter constructs (iNOS/eNOS-Luc) in a dose-dependent fashion in COS7 cells selectively transfected with ERbeta, but failed to influence ERalpha-mediated increase of iNOS/ eNOS-Luc.

17beta-estradiol attenuates the development of pressure-overload hypertrophy.

Background: Cardiac hypertrophy is an independent risk factor for cardiovascular morbidity and mortality in men and in women. Epidemiological studies indicate that estrogen replacement therapy is cardioprotective; the mechanisms involved in this process, however, are poorly understood. We therefore studied the effect of 17beta-estradiol (E(2)) on the development of pressure-overload hypertrophy.

Endothelial dysfunction and oxidative stress during estrogen deficiency in spontaneously hypertensive rats.

Background: Postmenopausal estrogen deficiency is associated with an increased cardiovascular risk, hypertension, and oxidative stress. Angiotensin type 1 (AT(1)) receptor regulation is involved in the pathogenesis of atherosclerosis. To characterize vascular function, oxidative stress, and AT(1) receptor regulation during estrogen deficiency, ovariectomized spontaneously hypertensive rats (SHR) were investigated in comparison with sham-operated animals and with ovariectomized rats receiving estrogen replacement therapy with 17beta-estradiol.

Angiotensin-converting enzyme (ACE) inhibition attenuates insulin-like growth factor-I (IGF-I) induced cardiac fibroblast proliferation.

The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin type 1 (AT(1)) receptor blockade on insulin-like growth factor-I (IGF-I) induced proliferation and immediate-early-gene expression of neonatal rat cardiac fibroblasts were investigated. Moreover the role of the IGF-I receptor (IGF-IR) in this process was evaluated. IGF-I (10(-9) - 10(-7) M) stimulated neonatal rat cardiac fibroblast growth in a dose-dependent fashion (maximum: 3.

Estrogen receptor alpha rapidly activates the IGF-1 receptor pathway.

Estrogen and insulin-like-growth factor 1 (IGF-1) are potent mitogenic stimuli that share important properties in the control of cellular proliferation. However, the coupling between the signaling cascades of estrogen receptors alpha and beta and the IGF-1 receptor (IGF-1R) is poorly understood. Therefore, we selectively transfected estrogen receptor alpha or beta in COS7 and HEK293 cells, which contain IGF-1R.

Single-channel activity and expression of atrial L-type Ca(2+) channels in patients with latent hyperthyroidism.

Patients with "latent hyperthyroidism" (suppressed thyroid-stimulating hormone and normal circulating thyroid hormones) are at risk to develop atrial fibrillation. In animal models, hyperthyroidism is associated with increased cardiac L-type Ca(2+) current. Therefore, we assessed L-type channel function and expression in right atria from patients undergoing cardiac surgery.

17 Beta-estradiol stimulates expression of endothelial and inducible NO synthase in rat myocardium in-vitro and in-vivo.

Objectives: NO production has been attributed to play a major role in cardiac diseases such as cardiac hypertrophy and cardiac remodeling after myocardial infarction which display significant gender-based differences. Therefore we assessed the effect of 17 beta-estradiol (E2) on estrogen receptor (ER) alpha and beta and endothelial and inducible NO synthase in neonatal and adult rat cardiomyocytes.

Methods: The presence of ER alpha and ER beta was demonstrated by immunofluorescence and western blot analysis as well as the expression pattern of inducible NO synthase (iNOS) and endothelial NOS (eNOS) in isolated cardiomyocytes from neonatal and adult rats.

Angiotensin converting enzyme inhibitors block mitogenic signalling pathways in rat cardiac fibroblasts.

We studied the effects of angiotensin converting enzyme (ACE) inhibitors on angiotensin II (Ang II) induced growth related signalling pathways in neonatal rat cardiac fibroblasts. In BrdU proliferation assays, Ang II (10(-9)-10(-7) M) stimulated cardiac fibroblast growth in a dose-dependent fashion (maximum at 10(-7) M, 5.22 +/- 0.

Differential effects of 17beta-estradiol on mitogen-activated protein kinase pathways in rat cardiomyocytes.

Cardiac myocytes contain functional estrogen receptors, however, the effect of estrogen on growth-related signaling pathways such as mitogen-activated protein kinases (MAPK) in the pathogenesis of cardiac disease is unclear. MAPKs are critically involved in regulatory signaling pathways which ultimately lead to cardiac hypertrophy. Here we show that 17beta-estradiol (E2) activates extracellular signal-regulated kinase (ERK1/2), c-Jun-NH2-terminal protein kinase (JNK) and p38 in rat cardiomyocytes in a distinctive pattern.

Induction of Egr-1 mRNA and protein by endothelin 1, angiotensin II and norepinephrine in neonatal cardiac myocytes.

The early growth response gene Egr-1 is a nuclear transcription factor known to serve as an intermediary in a broad range of signal transduction processes. Recent studies have assigned Egr-1 a new role as an amplifier of gene expression. Egr-1 mRNA is expressed in the myocardium and is rapidly induced in response to hypertrophic stimuli.

[MRT versus CT in the diagnosis of pneumonias: an evaluation of a T2-weighted ultrafast turbo-spin-echo sequence (UTSE)].

Purpose: To evaluate a T2-weighted URSE sequence for the assessment of pulmonary infiltrations in comparison to CT.

Methods: 28 MRT scans of 22 patients with confirmed pneumonia were recorded on a 1.5 Tesla apparatus with an expiratory and diastolic triggered, T2-weighted ultrafast-spin-echo sequence in axial slice mode with the following parameters: TReff/TE/Turbo-factor 2000-4000/90 ms/21-23; slice thickness/separation 6/0.

Rapid modulation of L-type calcium current by acutely applied oestrogens in isolated cardiac myocytes from human, guinea-pig and rat.

Gender-based differences in cardiovascular mortality may be due to a cardio-protective effect of oestrogens on the myocardium. However, mRNA expression of oestrogen receptors in myocardial tissue of the adult heart has yet to be demonstrated. Furthermore, a calcium antagonistic action of 17beta-oestradiol on myocardial tissue has been discussed.

Estrogen modulates AT1 receptor gene expression in vitro and in vivo.

Background: The AT1 receptor has been implicated in the pathogenesis of hypertension and atherosclerosis. Estrogen deficiency is also associated with cardiovascular diseases. Therefore, we examined the AT1 receptor gene expression in ovariectomized rats with and without estrogen replacement therapy and the influence of estrogen on AT1 receptor expression in cultured vascular smooth muscle cells.

Angiotensin converting enzyme inhibition modulates cardiac fibroblast growth.

Background: The progression of left ventricular hypertrophy and cardiac fibrosis in hypertensive heart disease is influenced by sex and age. Although angiotensin converting enzyme inhibition has been shown to prevent progression of the disease in postmenopausal women, the interaction of angiotensin II and estrogen in this process before and after the menopause is poorly understood.

Objective: To investigate the influence of the angiotensin converting enzyme inhibitor moexiprilat on serum, estrogen and angiotensin II-induced cardiac fibroblast growth.

Expression of oestrogen receptor alpha and beta in rat heart: role of local oestrogen synthesis.

The role of cardiac oestrogen receptor expression and local oestrogen synthesis in the pathogenesis of cardiovascular disease is poorly understood. Therefore we studied the effects of the oestrogen precursors androstendione and testosterone on the expression of cyp450 aromatase, oestrogen receptor alpha and beta, and inducible NO synthase (iNOS) in neonatal rat cardiac myocytes. Here, we show that cyp450 aromatase is expressed in cardiac myocytes and incubation of cardiac myocytes with oestrogen precursors leads to sexual dimorphic transactivation of an oestrogen-responsive reporter plasmid.

Cardiac myocytes and fibroblasts contain functional estrogen receptors.

Gender-based differences found in cardiovascular diseases raise the possibility that estrogen may have direct effects on cardiac tissue. Therefore we investigated whether cardiac myocytes and fibroblasts express functional estrogen receptors. Immunofluorescence demonstrated estrogen receptor protein expression in both female and male rat cardiac myocytes and fibroblasts.

Effects of moexiprilat on oestrogen-stimulated cardiac fibroblast growth.

1. The effects of 2-2-(1-(ethoxycarbonyl)-3-phenylpropyl)-[amino-oxopropyl]-6,7-dimethoxy- 1,2,3,4-tetrahydroisoquinoline-3 carboxylic acid (moexiprilat), 17beta-oestradiol (E2), oestrone (ES) and angiotensin II (AII) on growth and activation of oestrogen receptors and the immediate-early gene egr-1 were investigated in neonatal rat cardiac fibroblasts of female and male origin. 2.

Effects of estrogen on skeletal myoblast growth.

To determine the role of estrogen in skeletal muscle growth, we investigated estrogen receptor-mediated effects on proliferation in skeletal myoblasts. In L6, C2C12 and Sol8 myoblasts estrogen receptor was demonstrated by immunoblotting, immunofluorescence microscopy and transfection studies. Estrone induced a significant increase in myoblast growth whereas 17 beta-estradiol had no effect.

Modulation of hypertensive heart disease by estrogen.

Unlabelled: Left ventricular hypertrophy is an independent risk factor for morbidity and mortality in patients with hypertensive heart disease. Cardiac hypertrophy, associated with increased cardiac fibrosis and myocardial relaxation impairment, shows gender-based differences with significantly higher mortality in men. The role of estrogen in the pathogenesis of this process is poorly understood.

Hormonal induction of an immediate-early gene response in myogenic cell lines--a paradigm for heart growth.

Cardiac hypertrophy is characterized by growth of myocardial cells without proliferation. Many endo- paracrine stimuli such as angiotensin II, endothelin, alpha 1-adrenergic agonists, and insulin have been shown to be able to induce cardiac hypertrophy either in vivo or in vitro. We have used the myoblast model of differentiation and proliferation to determine nuclear signal transduction mechanisms in muscle and (by analogy) cardiac growth.

Mitogenic signals control translation of the early growth response gene-1 in myogenic cells.

Muscle is a major site of expression of the early growth response gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle Sol8 cells. Three groups of responses could be distinguished: 1.

Effects of nisoldipine on endothelin-1- and angiotensin II-induced immediate/early gene expression and protein synthesis in adult rat ventricular cardiomyocytes.

The cellular mechanisms by which dihydropyridine-type calcium antagonists lead to regression of hypertension-related cardiac hypertrophy have not been clarified. We previously showed that angiotensin II (AII) and endothelin-1 (ET-1) induce protein synthesis in isolated adult rat cardiomyocytes, probably through protein kinase C (PKC) as second messenger and the gene product of the early growth response gene-1 (Egr-1) as third messenger. We now show that the dihydropyridine derivative nisoldipine inhibits AII- and ET-1-induced protein synthesis at low concentrations (IC50 7.