Vitamin D receptors in heart: effects on atrial natriuretic factor.

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D3 (1,25-D3, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D3 suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D3 and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.     

Vitamin D receptors in heart: Effects on atrial natiuretic factor

We report that receptors for vitamin D exist in distinct regions of the heart in female and male mice, predominantly in the right atrium where most of the cardial atrial natriuretic peptide (ANF) is produced. Tritiated 1,25-dihydroxyvitamin D₃ (1,25-D₃, vitamin D, soltriol) and ANF are colocalized in nuclei and cytoplasm respectively in identical cardiomyocytes. Changes of ANF tissue and blood levels under dietary deficiency and treatment with 1,25-D₃ suggest direct genomic actions of vitamin D on myoendocrine cells of the atrium for the regulation of ANF manufacture and secretion. These results were obtained by combining thaw-mount autoradiography with immunocytochemistry using tritiated 1,25-D₃ and an antibody against rat ANF. This antibody was also used in a radioimmunoassay to determine atrial natriuretic factor in plasma, atria and ventricles of normal or vitamin D-deficient mice.     

Tbx2 and Tbx3 induce atrioventricular myocardial development and endocardial cushion formation

A key step in heart development is the coordinated development of the atrioventricular canal (AVC), the constriction between the atria and ventricles that electrically and physically separates the chambers, and the development of the atrioventricular valves that ensure unidirectional blood flow. Using knock-out and inducible overexpression mouse models, we provide evidence that the developmentally important T-box factors Tbx2 and Tbx3, in a functionally redundant manner, maintain the AVC myocardium phenotype during the process of chamber differentiation. Expression profiling and ChIP-sequencing analysis of Tbx3 revealed that it directly interacts with and represses chamber myocardial genes, and induces the atrioventricular pacemaker-like phenotype by activating relevant genes. Moreover, mutant mice lacking 3 or 4 functional alleles of Tbx2 and Tbx3 failed to form atrioventricular cushions, precursors of the valves and septa. Tbx2 and Tbx3 trigger development of the cushions through a regulatory feed-forward loop with Bmp2, thus providing a mechanism for the co-localization and coordination of these important processes in heart development.     

Uptake of noradrenaline in high altitude native's heart

Summary Uptake of³H-noradrenaline by the heart was studied with sections of isolated atria obtained from high or lowlanders. In native highlanders, affinity for³H-noradrenaline by human atria is more significant than in lowlanders. Furthermore, the Michaelis Menten constant is lower in high altitude native's heart.     

Quantitative changes in beta-adrenergic responses of isolated atria from hyper- and hypothyroid rats

Concentration-response curves for the chronotropic and inotropic effects of isoprenaline, in the absence and presence of propranolol, were obtained on heart atria isolated from normo- or dysthyroid rats. Hyperthyroidism increased the chronotropic potency and efficacy of the beta-adrenergic agonist. The results are compatible with the view that thyroid hormone increases the density of functional beta-adrenoceptors in cardiac pacemaker tissue.     

Close relation between hypothalamic and cardiac norepinephrine during stress and its role in acute myocardial infarction disrhythmias

Summary The decrease of the norepinephrine levels in hypothalamus and heart caused by stress is prevented by pargyline and imipramine. Such a decrease in spleen and adrenals is not affected. Chlorpromazine and lithium only prevent the norepinephrine decrease in the spleen. The uptake of H³norepinephrine by isolated atria of guinea-pig increases during anoxia; the change to a normal oxygen situation decreases these norepinephrine levels by more than 50%.     

Erratum to: Identification of functional differences between recombinant human α and β cardiac myosin motors

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is >ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding.     

Identification of functional differences between recombinant human α and β cardiac myosin motors

The myosin isoform composition of the heart is dynamic in health and disease and has been shown to affect contractile velocity and force generation. While different mammalian species express different proportions of α and β myosin heavy chain, healthy human heart ventricles express these isoforms in a ratio of about 1:9 (α:β) while failing human ventricles express no detectable α-myosin. We report here fast-kinetic analysis of recombinant human α and β myosin heavy chain motor domains. This represents the first such analysis of any human muscle myosin motor and the first of α-myosin from any species. Our findings reveal substantial isoform differences in individual kinetic parameters, overall contractile character, and predicted cycle times. For these parameters, α-subfragment 1 (S1) is far more similar to adult fast skeletal muscle myosin isoforms than to the slow β isoform despite 91% sequence identity between the motor domains of α- and β-myosin. Among the features that differentiate α- from β-S1: the ATP hydrolysis step of α-S1 is ~ten-fold faster than β-S1, α-S1 exhibits ~five-fold weaker actin affinity than β-S1, and actin·α-S1 exhibits rapid ADP release, which is >ten-fold faster than ADP release for β-S1. Overall, the cycle times are ten-fold faster for α-S1 but the portion of time each myosin spends tightly bound to actin (the duty ratio) is similar. Sequence analysis points to regions that might underlie the basis for this finding.     

Adenosine activates a potassium conductance in guinea-pig atrial heart muscle

Adenosine shortens the action potential and diminishes the force of contraction in guinea-pig left atria. These effects may be brought about by the activation of a potassium conductance. This assumption is supported by voltage clamp and 42K release experiments.     

Positive and negative inotropic effects of carbachol on the embryonic chick atrium.

The effect of carbachol on twitch tension of atrial preparations from chick embryos of different incubation ages (3-14 days) was studied. At every age carbachol evoked negative (at low concentrations) and positive (at higher concentrations) inotropic responses. Maximal response values for both effects increased with age; in 3- and 5-day atria the positive inotropic response prevailed. The muscarinic antagonist pirenzepine inhibited the positive (on 5-day atria) and negative (on strips of 14-day atria) inotropic effects of carbachol with pA2 values of 6.8 and 8.0, respectively, suggesting that muscarinic receptors mediating these effects belong to different receptor subtypes.     

Quantitative changes in β-adrenergic responses of isolated atria from hyper- and hypothyroid rats

Summary Concentration-response curves for the chronotropic and inotropic effects of isoprenaline, in the absence and presence of propranolol, were obtained on heart atria isolated from normo- or dysthyroid rats. Hyperthyroidism increased the chronotropic potency and efficacy of the -adrenergic agonist. The results are compatible with the view that thyroid hormone increases the density of functional -adrenoceptors in cardiac pacemaker tissue.This study was supported by the Swiss National Science Foundation grant No. 3.374.-0.78. We thank Dr Bachmann from the Central Laboratory of the University Hospital Bern for the estimation of plasma thyroxine levels.     

Positive and negative inotropic effects of carbachol on the embryonic chick atrium

The effect of carbachol on twitch tension of atrial preparations from chick embryos of different incubation ages (3–14 days) was studied. At every age carbachol evoked negative (at low concentrations) and positive (at higher concentrations) inotropic responses. Maximal response values for both effects increased with age; in 3- and 5-day atria the positive inotropic response prevailed. The muscarinic antagonist pirenzepine inhibited the positive (on 5-day atria) and negative (on strips of 14-day atria) inotropic effects of carbachol with pA₂ values of 6.8 and 8.0, respectively, suggesting that muscarinic receptors mediating these effects belong to different receptor subtypes.     

Wiederherstellung des normalen Herzschlages nach elektrisch erzeugtem Kammerflimmern durch Adenosintriphosphorsäure

Summary (1) In the isolated mammalian heart (rabbit, cat, dog) electrically induced ventricular fibrillation is stopped in practically 100% of the cases by adenosin-triphosphoric acid (ATP) in doses of 0.25–20 mg, and the normal rhythm of the heart is permanently restored (as far as the experiment extends).(2) This effect of ATP follows from a primary blocking, which leads to a complete cessation of the activity of the ventricles with diastolic dilatation of the heart.(3) In as much as adenyl acid from yeast and adenosin (in large doses) also stop ventricular fibrillation, the energetic effect of ATP seems to be of no importance in stopping it; it is a specific effect of the adenyl compounds on the bundle ofHis.     

Histones and heart failure in diabetes

Although heart failure is now accepted as being a major long-term complication of diabetes, many of the recent advances in our understanding of the pathobiology of diabetes complications have come about through the study of more traditional microvascular or macrovascular diseases. This has been the case, for example, in the evolving field of the epigenetics of diabetes complications and, in particular, the post-translational modification of histone proteins. However, histone modifications also occur in human heart failure and their perturbation also occurs in diabetic hearts. Here, we review the principal histone modifications and their enzymatic writers and erasers that have been studied to date; we discuss what is currently known about their roles in heart failure and in the diabetic heart; we draw on lessons learned from the studies of microvascular and macrovascular complications; and we speculate that therapeutically manipulating histone modifications may alter the natural history of heart failure in diabetes.     

Zur Entwicklung der Gefässe im Herzmuskel

Summary In the developing rat heart 3 periods may be distinguished with regard to the nutrition of the myocardium: (1) Nutrition by diffusion (up to the 12th embryonic day). (2) Period of venous circulation in which the blood passes from the ventricles through sinusoids, capillaries and veins to the coronary sinus. (3) The coronary circulation, which starts with the formation of coronary arteries. By the end of the first week of life, the cardiac circulating system is fully developed.     

Postnatal development of adrenergic and cholinergic sensitivity in the isolated rat atria

The sensitivity to adrenergic drugs in isolated rat atria increased with the postnatal development. The cholinergic chronotropic sensitivity did not further change after birth.     

Postnatal development of adrenergic and cholinergic sensitivity in the isolated rat atria

Summary The sensitivity to adrenergic drugs in isolated rat atria increased with the postnatal development. The cholinergic chronotropic sensitivity did not further change after birth.     

Opposite effects of beta-adrenoceptor stimulation and 8-bromo-cyclic AMP on potassium efflux in mammalian heart muscle

beta-adrenoceptor stimulation by isoprenaline increases the potassium efflux in beating guinea-pig atria. This effect is not mimicked by 8-bromo-cyclic AMP, a cyclic AMP analogue which exerts a positive inotropic effect in this preparation.