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Inotropic effects of histamine on developing chick heart: release of transmitters from autonomic nerve terminals.

Inotropic effects of histamine were examined in isolated ventricular preparations from late embryonic and hatched chick hearts. In 19 day-old embryonic preparations, histamine had little effect on the contractile force. In preparations from 1 to 2 day-old hatched chick, histamine produced a transient decrease in contractile force followed by a sustained increase. The negative and positive responses were antagonized by atropine and propranolol, respectively, but not by histamine antagonists terfenadine, cimetidine or thioperamide. Acetylcholine produced positive inotropic responses in the embryo while negative responses were observed after hatching. In myocardium of hatched chicks, compound 48/80, which releases histamine from mast cells, produced a transient decrease in contractile force followed by a sustained increase with a similar magnitude and time course to the case of exogenously applied histamine. The negative and positive responses were inhibited by atropine and propranolol, respectively, but not by terfenadine, cimetidine or thioperamide, which was similar to the case with the responses to histamine. The present results suggest that histamine, either applied exogenously or released from myocardial store sites, produces negative and positive inotropic responses in hatched chick myocardium which are due to release of acetylcholine and norepinephrine, respectively, from autonomic nerve terminals.

Acetylcholine↗

Changes in adrenergic receptors during the development of heart failure.

Moderate and severe stages of congestive heart failure due to the loss of myocardium upon coronary occlusion in rats was associated with an increase in alpha-adrenergic receptors and a decrease in beta-adrenergic receptors in the viable left ventricle. However, at early stages of heart failure the number of beta-adrenergic receptors was decreased without any changes in the number of alpha-adrenergic receptors. The affinities of these receptors to alpha receptor antagonist (3H-prazosin) and beta receptor antagonist (3H-dihydroalprenolol) were not altered in the failing hearts. On the other hand, the pattern of changes in both alpha- and beta-adrenergic receptors in heart membranes treated with oxygen free radical generating system was different from that seen in the failing hearts. In particular, the affinities for these receptors were decreased whereas the number of beta-receptors was increased and the number of alpha-receptors was decreased or unchanged. These results indicate that alterations in the adrenergic receptors in heart failure are not due to the formation of oxygen free radicals.

Animals↗

Kinetic changes of ethanolamine base exchange activity and increase of viscosity in sarcolemmal membranes of hamster heart during development of cardiomyopathy.

The activity of the phospholipid base exchange enzyme specific for ethanolamine has been measured in cardiac sarcolemmal membrane preparations from Syrian golden and UM-X7.1 cardiomyopathic hamsters. In Syrian golden hamsters, the Km of the enzyme for ethanolamine does not change with age, whereas it almost doubles in membranes from cardiomyopathic animals, from the 30th to the 150th day of age. During the same period, the membrane cholesterol content increases by 68% in cardiomyopathic hamsters, whereas it does not change significantly in the Syrian golden hamster strain. As a consequence, in the adult animal, the cholesterol to phospholipid ratio and the viscosity of sarcolemmal membranes are higher in UM-X7.1 strain than in Syrian golden hamsters. A cause-consequence relationship between the enzymatic changes and the compositional modifications in the sarcolemma occurring in UM-X7.1 hamsters during the development of cardiomyopathy is proposed.

Animals↗

Postnatal development of heart rate patterns elicited by an aversive CS and US in cats.

Heart rate and motor responses were recorded in cats of different ages during classical conditioning. A deceleratory-acceleratory heart rate pattern observed during the CS-US interval in one- and four-week-old kittens is an alpha conditioned response, a potentiated original response to the CS. At eight weeks of age two new distinct patterns of pure acceleration or pure deceleration are acquired during conditioning and in the absence of motor learning. At 12 weeks of age and in adult subjects, heart rate patterns during the CS-US interval become more complex and conditioned motor responses can be observed. A covariance of HR acceleration and motor responses during the CS-US interval is absent in eight-week-old subjects, but quite high in 12-week-old subjects and adult cats. The data are interpreted as suggesting separate elicitatory mechanisms of HR and motor responses which may show synchrony later in ontogeny.

Age Factors↗

Transgenic expression of CECR1 adenosine deaminase in mice results in abnormal development of heart and kidney.

Cat eye syndrome is a rare developmental defect associated with duplication of chromosome 22q11. The patients demonstrate specific abnormalities of heart, kidney, and eye. Here we attempted to produce a model for this defect by expressing CECR1 adenosine deaminase, a gene duplicated in cat eye syndrome patients, in mice. The transgenic mice expressed CECR1 under the control of either beta-actin promoter for ubiquitous expression or myosin heavy chain for heart-specific expression. The transgenics expressing CECR1 in the heart demonstrated high rate of embryonic and neonatal lethality. The mice from all the lines examined showed enlargement of the heart. Abnormalities of the kidney and eye were also detected in mice expressing CECR1 under control of the actin promoter.

Actins↗

Soy protein, isoflavonoids, and risk of developing coronary heart disease.

The effects of soy protein and isoflavones on blood cholesterol in humans has been variable. Maximal low- density lipoprotein cholesterol lowering appears to be modest and consistently ranges from 5% to 7%. Preliminary evidence suggests a potentially beneficial effect of the isoflavone fraction of soybeans on arterial compliance. The isoflavone fraction has been demonstrated to decrease the in vitro susceptibility of low-density lipoprotein to oxidation; the significance of this finding in vivo is unknown. It is difficult to definitively say at this time whether increased consumption of soy based products will result in a decreased risk of CHD beyond their ability to displace foods high in saturated fat and cholesterol from the diet.

Cholesterol, LDL↗

Stimulation of phosphoinositide hydrolysis and inhibition of cyclic AMP formation by muscarinic agonists in developing chick heart.

As early as 4 days in ovo, phosphoinositide hydrolysis in embryonic chick heart was stimulated by the cholinergic agonist carbachol. In the 4-day chick heart, the concentrations of carbachol giving half-maximal and maximal stimulation of [3H]inositol 1-phosphate formation were 30 microM and 1 mM respectively. These values are identical to those obtained using hearts from 13-day embryos [J. H. Brown and S. L. Brown, J. biol. Chem. 259, 3777 (1984)]. The amounts of [3H]inositol 1-phosphate formed per mg protein in the presence of carbachol were greater at early ages than at later ones; the stimulation by carbachol thus decreased from 8-fold at 4 days to 2-fold at 13 days. Muscarinic receptor stimulation also led to inhibition of isoproterenol-stimulated cyclic AMP formation as early as 4 days. The isoproterenol-stimulated increase in cyclic AMP was greatest at early ages, whereas the inhibitory effect of carbachol remained constant at 75%. At 4 days, half-maximal and maximal inhibition by carbachol occurred at 0.3 and 30 microM, respectively, the same values obtained using 13-day hearts (see reference cited above). Thus, the two biochemical responses of embryonic chick heart to muscarinic agonists have identical agonist sensitivities regardless of embryonic age and are functional prior to parasympathetic innervation and physiological responsiveness.

Animals↗

Alterations in sarcoplasmic reticulum calcium uptake, relaxation parameters and their responses to beta-adrenergic agonists in the developing rabbit heart.

Developmental changes in cardiac sarcoplasmic reticulum function, which may reflect alterations in the myocardial rate of relaxation and its responses to beta-adrenergic stimulation, were assessed using fetal, 4-day-old, 21-day-old and adult rabbit hearts. The fetal hearts exhibited the slowest rate of relaxation (-dP/dt) and the lowest Vmax and EC50 of the sarcoplasmic reticulum Ca(2+)-pump for Ca2+ compared to the other age groups. These parameters were similar among the 4-day-old, 21-day-old and adult hearts. The low physiological and biochemical parameters in the fetal hearts reflected reduced levels of expression of the sarcoplasmic reticulum Ca(2+)-pump and its inhibitor, phospholamban, assessed by quantitative immunoblotting. Isoproterenol perfusion of fetal hearts had no significant effect on their relaxation parameters or on the EC50 of the Ca(2+)-pump for Ca2+, consistent with the low relative levels of phospholamban expressed in these hearts. However, perfusion of the 4-day-old, 21-day-old and adult hearts with isoproterenol resulted in significant increases in the rates of relaxation of each group. The increases in relaxation parameters were associated with decreases in the EC50 of the cardiac sarcoplasmic reticulum Ca(2+)-pump for Ca2+, suggesting a phosphorylation-mediated relief of the phospholamban inhibitory effects. These findings indicate that developmental regulation of the levels of the activity of the cardiac sarcoplasmic reticulum Ca(2+)-pump may reflect alterations in cardiac relaxation parameters and their modulation by beta-adrenergic agonists.

Adrenergic beta-Agonists↗