Characterization of the histamine receptors in rabbit left atria

1981 ◽  
Vol 59 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Alicia Polanin ◽  
John H. McNeill
Keyword(s):  
Left Atrial ◽  
Histamine Receptor ◽  
Histamine Receptors ◽  
Receptor Blockade ◽  
Inotropic Response ◽  
Receptor Stimulation ◽  
Inotropic Effects ◽  
Receptor Antagonism ◽  
Positive Inotropic Effects

The effects of selective histamine receptor analogs were studied in electrically paced rabbit left atria. Atrial tension was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA) (an H1 agonist). The responses to histamine and impromidine were not altered by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the responses to 4-methylhistamine and PEA were significantly decreased upon pretreatment with propranolol or reserpine. Promethazine pretreatment (H1 receptor blockade) antagonized the inotropic effects of histamine and PEA but had no effect on the responses to 4-methylhistamine or impromidine. Cimetidine pretreatment (H2 receptor antagonism) competitively blocked the positive inotropic effects of histamine, 4-methylhistamine, and impromidine. These results suggest that the left atrial inotropic response is mediated through H1 and H2 receptor stimulation.

Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations

2000 ◽  
Vol 279 (2) ◽  
pp. H702-H708 ◽  
Author(s):  
Hans-Peter Hermann ◽  
Oliver Zeitz ◽  
Boris Keweloh ◽  
Gerd Hasenfuss ◽  
Paul M. L. Janssen
Keyword(s):  
Energy Demand ◽  
Contractile Force ◽  
Potential Importance ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Individual Effects ◽  
Positive Inotropic Effects ◽  
Series Of Experiments ◽  
The Individual ◽  
Mere Addition

Catecholamines and elevated extracellular Ca2+concentration ([Ca2+]o) augment contractile force by increased Ca2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca2+ release. We tested the hypothesis that pyruvate potentiates Ca2+ release and inotropic response to isoproterenol and elevated [Ca2+]o, since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca2+]o of 1.25 mM, pyruvate (10 mM) alone increased developed force (Fdev) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm2 ( n = 8, P < 0.05) and isoproterenol (10−6 M) alone increased Fdev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm2 ( P < 0.05), whereas the combination of isoproterenol and pyruvate increased Fdevoverproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm2 ( P < 0.05). In a separate series of experiments, we assessed SR Ca2+ content by means of rapid cooling contractures and observed that, despite no further increase in Fdev by increasing [Ca2+]o from 8 to 16 mM, 10 mM pyruvate could still increase Fdev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm2( P < 0.05, n = 9) as well as the Ca2+ load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca2+, because in the presence of pyruvate, Ca2+ and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.

scholarly journals Amitriptyline functionally antagonizes cardiac H2 histamine receptors in transgenic mice and human atria

2021 ◽  
Author(s):  
Joachim Neumann ◽  
Maximilian Benedikt Binter ◽  
Charlotte Fehse ◽  
Margaréta Marušáková ◽  
Maren Luise Büxel ◽  
...  
Keyword(s):  
Antidepressant Drug ◽  
Histamine Receptor ◽  
Right Atrial ◽  
Inotropic Effects ◽  
Positive Inotropic Effects ◽  
Contractile Parameters ◽  
Left And Right ◽  
Chronotropic Effects ◽  
Perfused Hearts ◽  
Right Atria

AbstractWe have previously shown that histamine (2-(1H-imidazol-4-yl)ethanamine) exerted concentration-dependent positive inotropic effects (PIE) or positive chronotropic effects (PCE) on isolated left and right atria, respectively, of transgenic (H2R-TG) mice that overexpress the human H2 histamine receptor (H2R) in the heart; however, the effects were not seen in their wild-type (WT) littermates. Amitriptyline, which is still a highly prescribed antidepressant drug, was reported to act as antagonist on H2Rs. Here, we wanted to determine whether the histamine effects in H2R-TG were antagonized by amitriptyline. Contractile studies were performed on isolated left and right atrial preparations, isolated perfused hearts from H2R-TG and WT mice and human atrial preparations. Amitriptyline shifted the concentration-dependent PIE of histamine (1 nM–10 μM) to higher concentrations (rightward shift) in left atrial preparations from H2R-TG. Similarly, in isolated perfused hearts from H2R-TG and WT mice, histamine increased the contractile parameters and the phosphorylation state of phospholamban (PLB) at serine 16 in the H2R-TG mice, but not in the WT mice. However, the increases in contractility and PLB phosphorylation were attenuated by the addition of amitriptyline in perfused hearts from H2R-TG. In isolated electrically stimulated human atria, the PIE of histamine that was applied in increasing concentrations from 1 nM to 10 μM was reduced by 10-μM amitriptyline. In summary, we present functional evidence that amitriptyline also acts as an antagonist of contractility at H2Rs in H2R-TG mouse hearts and in the human heart which might in part explain the side effects of amitriptyline.

Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions

2002 ◽  
Vol 283 (5) ◽  
pp. H2045-H2053 ◽  
Author(s):  
Manabu Nishio ◽  
Stuart W. Ruch ◽  
J. Andrew Wasserstrom
Keyword(s):  
Atpase Activity ◽  
Voltage Clamp ◽  
Ventricular Myocytes ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Cellular Effects ◽  
Positive Inotropic Effects ◽  
Intracellular Ca ◽  
Atpase Inhibition ◽  
External K

The inotropic and toxic effects of cardiac steroids are thought to result from Na+-K+-ATPase inhibition, with elevated intracellular Na+(Na[Formula: see text])causing increased intracellular Ca2+(Ca[Formula: see text]) via Na-Ca exchange. We studied the effects of ouabain on cat ventricular myocytes in Na+-free conditions where the exchanger is inhibited. Cell shortening and Ca[Formula: see text] transients (with fluo 4-AM fluorescence) were measured under voltage clamp during exposure to Na+-free solutions [LiCl or N-methyl-d-glucamine (NMDG) replacement]. Ouabain enhanced contractility by 121 ± 55% at 1 μmol/l ( n = 11) and 476 ± 159% at 3 μmol/l ( n = 8) (means ± SE). Ca[Formula: see text] transient amplitude was also increased. The inotropic effects of ouabain were retained even after pretreatment with saxitoxin (5 μmol/l) or changing the holding potential to −40 mV (to inactivate Na+ current). Similar results were obtained with both Li+ and NMDG replacement and in the absence of external K+, indicating that ouabain produced positive inotropy in the absence of functional Na-Ca exchange and Na+-K+-ATPase activity. In contrast, ouabain had no inotropic response in rat ventricular myocytes (10–100 μmol/l). Finally, ouabain reversibly increased Ca2+overload toxicity by accelerating the rate of spontaneous aftercontractions ( n = 13). These results suggest that the cellular effects of ouabain on the heart may include actions independent of Na+-K+-ATPase inhibition, Na-Ca exchange, and changes in Na[Formula: see text].

Significance of the endothelin ETA receptor in the haemodynamic and inotropic effects of endothelin-1 in rats

2004 ◽  
Vol 107 (5) ◽  
pp. 467-475 ◽  
Author(s):  
Martin E. BEYER ◽  
Tobias HÖVELBORN ◽  
Ursula DELABAR ◽  
Hans Martin HOFFMEISTER
Keyword(s):  
Cardiac Output ◽  
Positive Inotropic Effect ◽  
Peripheral Resistance ◽  
Inotropic Effect ◽  
Receptor Blockade ◽  
Atp Content ◽  
Receptor Stimulation ◽  
Inotropic Effects ◽  
Eta Receptor ◽  
Etb Receptor

The main aim of the present study was to investigate the direct inotropic effects of stimulation of the endothelin (ET) receptor ETA under in vivo conditions. It is well known that ETA receptor stimulation causes pronounced vasoconstriction. The ET-1-induced coronary vasoconstriction may lead to myocardial ischaemia and, consequently, to cardiodepressor effects that may mask the direct positive inotropic effect of ETA receptor stimulation. Thus, in the present study, steps were taken to avoid this possibility. In anaesthetized open-chest rats the haemodynamic and inotropic effects of ETA receptor stimulation were studied by monitoring responses evoked by ET-1 (1 nmol/kg of body weight) after ETB receptor blockade with BQ 788 (0.5 μmol/kg of body weight); these responses were compared with saline controls (after ETB receptor blockade). To avoid vasoconstrictor effects induced by ETA receptor stimulation, additional experiments were performed in the presence of the vasodilator adenosine (2.0 mg·kg−1 of body weight·min−1). Myocardial function was also examined during aortic clamping so as to circumvent the effect of changes in afterload. We studied further the effect of ETA receptor stimulation on myocardial energy metabolism. ETA receptor stimulation reduced cardiac output (−49% compared with control), raised total peripheral resistance (+173%) and reduced myocardial ATP content (−23%). Aortic clamping did not reveal a positive inotropic effect of ETA receptor stimulation. Furthermore, even though adenosine attenuated the decrease in cardiac output (−21%), the increase of total peripheral resistance (+48%) and prevented the fall of myocardial ATP content (+6%), this did not unmask a positive inotropic effect of ETA receptor stimulation. Thus we conclude that ETA receptor stimulation causes vasoconstriction and myocardial ischaemia, but has no positive inotropic effects in rats.

The characterization of cardiac histaminergic chronotropic receptors in the rabbit

1981 ◽  
Vol 59 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Alicia Polanin ◽  
Thomas E. Tenner Jr. ◽  
John H. McNeill
Keyword(s):  
Histamine Receptor ◽  
Receptor Blockade ◽  
Chronotropic Response ◽  
Atrial Rate ◽  
Chronotropic Effects ◽  
Rabbit Atria ◽  
Stimulation Of

The effects of selective histamine receptor analogs were studied in spontaneously beating rabbit atria. Atrial rate was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA, an H1 agonist). The responses to histamine, 4-methylhistamine, and impromidine were not affected by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the response to PEA was nearly abolished upon pretreatment with propranolol or reserpine.Cimetidine pretreatment (H2 receptor blockade) competitively antagonised the positive chronotropic effects of histamine, 4-methylhistamine, and impromidine. Promethazine pretreatment (H1 receptor blockade) competitively blocked the chronotropic effects of histamine but had no effect on the responses to 4-methylhistamine or impromidine. These results suggest that stimulation of H1 and H2 receptors will cause a positive chronotropic response.

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