Rat Heart Atria Research Articles

Cellular mechanism of release of atrial natriuretic factor

Tissue extracts of rat heart atria contain a family of peptides with natriuretic and vasorelaxant properties. We have shown previously that this “atrial natriuretic factor” may be released in vitro from incubated atria by muscarinic cholinergic stimulation. Experiments reported here demonstrate that incubation with adrenalin or arginine vasopressin, but not with deamino-8-D-arginine vasopressin, also results in liberation of atrial natriuretic factor. Since the effective agonists have in common activation of the cellular polyphosphoinositide system with consequent production of inositol triphosphate, we suggest that inositol triphosphate is the second messenger of stimulus-secretion coupling in atrial cells.

Atrial pronatriodilatin: a precursor for natriuretic factor and cardiodilatin: Amino acid sequence evidence

Numerous peptides isolated from rat heart atria, including two containing 33 and 73 amino acids, were isolated and shown to exhibit natriuretic activities. Here, we describe the purification and partial amino acid sequence of a 106-residue peptide containing the previously sequenced 33- and 73-amino-acid ANF peptides. The determined sequence is a novel one and is not significantly homologous to any known protein or segment thereof. In fact, this sequence shows significant homology only to another novel partial sequence obtained from sequence analysis of a porcine peptide, called cardiodilatin, also found in heart atria. This relationship is taken as evidence that ANF and cardiodilatin are part of the same precursor molecule which would contain at the very least 126 amino acids.

Differences in the content and turnover of noradrenaline in rat heart atria and ventricles and circadian-phase-dependency.

In light-dark-synchronized male rats the levels of noradrenaline in heart atria were about 3 times that found in heart ventricles. Noradrenaline turnover rate which were about 8-9 fold greater for the atria than for the ventricles displayed a circadian-phase-dependency with increased rates in the dark period in both parts of the rat heart.

A comparison of the rates of protein synthesis and content of RNA between rat heart atria and ventricles: David M. Smith, Peter H. Sugden. Department of Cardiac Medicine, Cardiothoracic Institute, London W1N 2DX, England

A comparison of the rates of protein synthesis and content of RNA between rat heart atria and ventricles: David M. Smith, Peter H. Sugden. Department of Cardiac Medicine, Cardiothoracic Institute, London W1N 2DX, England

An ultrastructural study of the effects of age on sympathetic innervation and atrial tissue in the rat.

Previous work on the rat heart has demonstrated an age-related reduction in catecholamines and a decline in myocardial cell sensitivity to catecholamines in vitro. We used ultrastructural cytochemical techniques to label noradrenergic vesicles of the sympathetic nerve terminals of the rat heart atrium, and addressed the question of whether these deficits are accompanied by a decrease in the number of synaptic vesicles or by progressive axonal degeneration. Our results demonstrate a significant sympathetic axonal degeneration between 3 and 24 months of age. No decrease in noradrenergic vesicle population in the intact nerve terminals could be discerned over this age span. Atrial cell structural alterations observed with age include: (1) increased quantities of residual bodies; (2) infrequent but definite myofibrillar disorganization at cell peripheries; (3) infrequent regional discontinuity of cell attachments and (4) increased extracellular collagen. We suggest that the apparent integrity of noradrenergic vesicle populations is consistent with reports by other investigators that levels of the catecholamine synthesizing enzyme, tyrosine hydroxylase, in sympathetic ganglia increase with age. The previously observed decline in cardiac catecholamines with age may be due to axonal degeneration rather than to reduced noradrenergic vesicles in intact terminals.

Differences in the fatty acid composition of atrial and ventricular phospholipids of rat heart following standard and lipid-supplemented diets

1. 1. The major saturated fatty acids of the phospholipids of rat heart atria and ventricles are similar and are not greatly altered by supplementing the diet with widely different types of lipid. 2. 2. There are important differences in the relative proportions of the major unsaturated fatty acids of the phospholipids of these anatomically and functionally distinct regions of the heart. 3. 3. The proportions of linoleic (C18:2, η-6) and docosahexaenoic (C22:6, η-3) acid are significantly higher in the ventricles than in the atria; the proportions of oleic (C18:1, η-9) arachidonic (C20:4, η-6) and docosatetraenoic acids (22:4, η-6) are higher in atria. 4. 4. The differences in unsaturated fatty acid profiles persist even after twelve months of feeding lipid supplements of sunflower seed oil (SSO) or sheep kidney (perirenal) fat (SKF). 5. 5. However, the ratios of arachidonic to docosahexaenoic acid in both tissues are changed by decreasing the intake of linoleic acid, which apparently favours the conversion of dietary linolenic (C18:3, η-3) to docosahexaenoic acid. The level of docosahexaenoic acid is greater in the ventricles than in the atria, and greatest when the animals were fed SKF diet. 6. 6. The physiological and pharmacological differences in ventricles and atria may arise from differences as fundamental as the phospholipid fatty acid composition of cardiac membranes.

Cardiac atrial factor--an endogenous diuretic?

An extract of rat heart atria causes a saluresis in bioassay rats. When organic acid secretion in the proximal tubule was blocked by probenecid, the saluretic response to the extract was significantly reduced. Similarly, the natriuretic response to acute hypervolemia was reduced by probenecid administration. The data indicate that the atrial natriuretic factor, like the "loop" diuretic drugs, requires proximal tubular secretion for maximal renal activity. Furthermore, the factor may play a role in the renal response to acute blood volume expansion.

Synthesis, redox characteristics, and in vitro norepinephrine uptake inhibiting properties of 2-(2-mercapto-4,5-dihydroxyphenyl)ethylamine (6-mercaptodopamine).

In an attempt to further characterize the structural features of 6-hydroxydopamine analogues that are associated with in vivo neuronal degeneration, the synthesis of 6-mercaptodopamine was undertaken. Although reaction conditions leading to the 1,4 addition of thiols to the model quinone 4-methyl-o-benzoquinone were achieved, attempts to obtain 6-thiolated dopamine analogues by this route failed. The synthesis of 6-mercaptodopamine was achieved by the regioselective thiocyanation of O,O-dimethyldopamine, followed by bis-O-demethylation and reductive cleavage of the S-cyano group. Unlike 6-hydroxydopamine, 6-mercaptodopamine was resistant to autoxidation at pH 7.4. Cyclic voltammometric analysis, however, indicated that electrochemically generated oxidation species of 6-mercaptodopamine are unstable and undergo spontaneous reaction, presumably intramolecular cyclization. In vivo tests revealed that 6-mercaptodopamine inhibits the uptake of tritium-labeled norepinephrine by isolated rat heart atria, although to a much lesser extent than 6-hydroxydopamine.

Renin-like activity in rat heart atria: J.M. Rojo-Ortega, A. J. de Bold and S.A. Bencosme. Clinical Research Institute of Montreal and Department of Pathology, Queen's University, Kingston, Ontario, Canada

Renin-like activity in rat heart atria: J.M. Rojo-Ortega, A. J. de Bold and S.A. Bencosme. Clinical Research Institute of Montreal and Department of Pathology, Queen's University, Kingston, Ontario, Canada

Long-term effects of N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride on noradrenergic neurones in the rat brain and heart.

1 N-2-Chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4) 50 mg/kg intraperitoneally, produced a long-term decrease in the capacity of brain homogenates to accumulate noradrenaline with significant effect 8 months after the injection. It had no effect on the noradrenaline uptake in homogenates from the striatum (dopamine neurones) and on the uptake of 5-hydroxytryptamine (5-HT) in various brain regions. 2 In vitro DSP 4 inhibited the noradrenaline uptake in a cortical homogenate with an IC50 value of 2 muM but was more than ten times less active on the dopamine uptake in a striatal homogenate and the 5-HT uptake in a cortical homogenate. 3 DSP 4 (50 mg/kg i.p.) inhibited the uptake of noradrenaline in the rat heart atrium in vitro but this action was terminated within 2 weeks. 4 DSP 4 (50 mg/kg i.p.) cuased a decrease in the dopamine-beta-hydroxylase (DBH) activity in the rat brain and heart. The onset of this effect was slow; in heart a lag period of 2-4 days was noted. In brain the DBH-activity in cerebral cortex was much more decreased than that in hypothalamus which was only slightly affected. A significant effect was still found 8 months after the injection. The noradrenaline concentration in the brain was greatly decreased for at least two weeks, whereas noradrenaline in heart was only temporarily reduced. 5 The long-term effects of DSP 4 on the noradrenaline accumulation, the DBH activity and noradrenaline concentration in the rat brain were antagonized by desipramine (10 mg/kg i.p.). 6 It is suggested that DSP 4 primarily attacks the membranal noradrenaline uptake sites forming a covalent bond and that the nerve terminals, as a result of this binding, degenerate.

A sensitive enzymatic-isotopic method for the analysis of tyramine in brain and other tissues.

Abstract— An enzymatic‐isotopic assay for the measurement of tyramine with a sensitivity of 1.0 ng has been developed. Using this assay, the endogenous content of tyramine in various tissues from adult rats has been determined. The highest tyramine content was found in rat heart atria, followed by salivary gland, kidney, and brain. Within the brain the distribution of tyramine is heterogeneous and the highest tyramine content was localized in the striatum.

On the mechanism of the accumulation of 3H-bretylium in peripheral sympathetic nerves.

The uptake of bretylium-(N-3H-methyl) iodide in the rat heart atrium in vitro was examined. The uptake was linear for at least 1 hr and was strongly inhibited by (+)-amphetamine, (-)-noradrenaline, desipramine, cocaine, DSP 4 [N-(2-bromobenzyl)-N-(2-chloroethyl)ethylamine hydrochloride], guanethidine and ouabain. The amphetamine sensitive part of the uptake was almost completely abolished by pre-treatment of the rats with 6-hydroxydopamine and was dependent on the presence of sodium ions. Reserpine had no effect. (+)-Amphetamine but not desipramine caused an increase of the efflux of bretylium from the tissue. The apparent Km value of the active bretylium uptake was 3 x 10(-6) M, which was 10 times higher than that of the uptake of (-)-noradrenaline in the rat heart atrium (Km = 3 x 10(-7) M). The inhibition constants (Ki) for bretylium in inhibiting the noradrenaline uptake and for (-)-noradrenaline in inhibiting the bretylium uptake were 7 x 10(-6) M and 4 x 10(-7) M, respectively. The results obtained support the hypothesis that bretylium is taken up by the same mechanism as that carrying noradrenaline into the nerve terminals but is not bound in the noradrenaline storage vesicles.

The inducible alkaline phosphatase of rat heart: Partial purification of the enzyme and its substrate specificity

The activity of an alkaline phosphatase in the right atrium of rat heart is enhanced by administration of catecholamines or their analogues. The enzyme has been partially purified from the atria of isoproterenol-treated animals and its substrate specificity has been investigated. It hydrolyses inorganic pyrophosphate and ATP besides orthophosphates such as p-nitrophenyl phosphate and β-glycerophosphate. Between pH 7 and 8, the rates of hydrolysis of inorganic pyrophosphate and p-nitrophenyl phosphate are similar, whereas at more alkaline pH values orthophosphatase activity predominates. The ratio of activities of the atrial phosphatase towards various substrates resembles that for analogous enzymes from other vertebrate tissues such as liver or kidney.

Rat atrial alkaline phosphatase activity and its response to isoprenaline (isoproterenol) during postnatal development

The right atrium of mature rat heart contains approximately three times as much alkaline phosphatase activity as the left atrium. Injection of isoprenaline (isoproterenol) is followed by a threefold rise in the right atrial phosphatase activity 7 h after injection, with a smaller rise in activity in the left atrium. Atrial phosphatase activity is first detectable histochemically 18 days after birth. Activities measured in extracts of atria show a difference between right and left atria at 25 days, and the pronounced response of the right atrial activity to injection of isoprenaline is established by the 49th day. These changes may be related to the development of atrial adrenergic innervation.

Release of acetylcholine by the isolated rat heart atria and its influence on regulation of contractility by rhythm.

Release of acetylcholine by the isolated rat heart atria and its influence on regulation of contractility by rhythm.

Electrolyte content of rat heart atria and ventricles.

Extracellular tissue spaces are compared using inulin, sucrose, chloride and sodium in hearts perfused with Ringer-Locke solution by Langendorff's method. Also chloride and sodium spaces are given for unperfused, fresh hearts. From the inulin spaces the intracellular chloride, sodium, potassium and water concentrations in both perfused and unperfused heart chambers have been calculated. Data showing the specificity of the atrium and ventricles of the heart are presented.