Further characterization of the receptors involved in the positive inotropic effect of histamine on rabbit papillary muscle

1986 ◽  
Vol 64 (12) ◽  
pp. 1484-1488 ◽  
Author(s):  
Alejandro Elizalde ◽  
Jesús Perez-Chavez ◽  
José Sánchez-Chapula
Keyword(s):  
Action Potentials ◽  
Positive Inotropic Effect ◽  
Phosphodiesterase Inhibitor ◽  
Adenosine Monophosphate ◽  
Inotropic Effect ◽  
Slow Inward Current ◽  
Force Of Contraction ◽  
Inotropic Effects ◽  
Slow Action Potentials ◽  
Stimulation Of

The effects of histamine on the force of contraction and calcium-dependent action potentials were studied in rabbit ventricular papillary muscles. The positive inotropic effect of histamine seems to be dependent on stimulation of H1 and H2 receptors. The H1 antagonist chlorpheniramine produced a competitive blockade of the positive inotropic effects of histamine. Cimetidine produced a competitive blockade, which was apparent only after blockade of H1 receptors. Histamine increased the maximum upstroke velocity of slow action potentials. This effect can be entirely accounted for by stimulation of H2 receptors. The phosphodiesterase inhibitor 3-isobutyl-methyl-xanthine potentiated the H2 receptor mediated effects of histamine on the force of contraction and slow action potentials. We conclude that rabbit ventricular muscle possesses both H1 and H2 receptors that mediate the positive inotropic effect of histamine. The H2-mediated effect seems to be causally related to an increase in the calcium slow inward current and is probably linked to an enhanced cellular cyclic adenosine monophosphate content. The mechanism of the H1-mediated positive inotropic effect remains unknown.

scholarly journals In Vitro Negative Inotropic Effect of Low Concentrations of Bupivacaine Relates to Diminished Ca2+ Sensitivity but Not to Ca2+ Handling or β-Adrenoceptor Signaling

2018 ◽  
Vol 128 (6) ◽  
pp. 1175-1186 ◽  
Author(s):  
Frederik Flenner ◽  
Nicole Arlt ◽  
Mahtab Nasib ◽  
Sophie Schobesberger ◽  
Thea Koch ◽  
...  
Keyword(s):  
Ion Channels ◽  
Local Anesthetics ◽  
Action Potentials ◽  
Cyclic Adenosine Monophosphate ◽  
Negative Inotropic Effect ◽  
Adenosine Monophosphate ◽  
Inotropic Effect ◽  
Dependent Manner ◽  
Half Maximum ◽  
Inotropic Effects

Abstract Background Systemic toxicity of local anesthetics is predominantly complicated by their myocardial toxicity. Especially long-acting local anesthetics exert a negative inotropic effect that has been described at lower concentrations than defined for blockade of myocardial ion channels. We evaluated the negative inotropic effect of bupivacaine at a concentration described for clinical toxicity testing the hypothesis that negative inotropy is a result of reduced Ca2+ sensitivity rather than blockade of ion channels. Methods We simultaneously measured force development and action potentials in guinea pig right papillary muscles (n = 5 to 7). L-type Ca2+ currents (n = 8 to 16) and Ca2+ transients (n = 10 to 11) were measured in isolated cardiomyocytes. Sensitivity of myofilaments to Ca2+ was assessed in skinned fibers (n = 10). Potential effects of bupivacaine on 3′,5′-cyclic adenosine monophosphate concentrations were measured using Förster Resonance Energy Transfer (n = 12 to 14) microscopy. Results Bupivacaine reduced force in a concentration-dependent manner from 173 ± 119 µN at baseline to 28 ± 13 µN at 300 µM (mean ± SD). At concentrations giving half-maximum negative inotropic effects (5 µM), the maximum upstroke velocity of action potentials, as a surrogate of sodium channel activity, was unaffected. Maximum positive inotropic effects of isoprenaline were also reduced to 50%. Neither basal nor isoprenaline-induced 3′,5′-cyclic adenosine monophosphate accumulation, L-type Ca2+ currents, or Ca2+ transients were affected by 5 µM bupivacaine, but this concentration significantly decreased Ca2+ sensitivity of myofilaments, changing the negative logarithm of the half-maximum effective Ca2+ concentrations from 5.66 to 5.56 –log[M]. Conclusions We provide evidence that the negative inotropic effect of bupivacaine may be caused mainly by a reduction in myofilament sensitivity to Ca2+.

Xenon Does Not Impair the Responsiveness of Cardiac Muscle Bundles to Positive Inotropic and Chronotropic Stimulation

2002 ◽  
Vol 96 (2) ◽  
pp. 422-427 ◽  
Author(s):  
Sylvia C. Schroth ◽  
Ulrich Schotten ◽  
Orkide Alkanoglu ◽  
Matthias S. Reyle-Hahn ◽  
Peter Hanrath ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Control Group ◽  
Control Force ◽  
Ventricular Muscle ◽  
Force Of Contraction ◽  
Inotropic Effects ◽  
Contraction Times

Background Most volatile anesthetics exhibit a direct myocardial depressant effect. This side effect often limits their applicability in patients with impaired cardiac function. Xenon is a new gaseous anesthetic that did not show any adverse cardiovascular effects in clinical and experimental studies. The authors tested the hypothesis that xenon does not affect myocardial contractility or the positive inotropic effect of isoproterenol, calcium, and increase in pacing rate in isolated guinea pig ventricular muscle bundles. Methods Thin ventricular muscle bundles from guinea pig hearts with a mean diameter of 0.4-0.45 mm were prepared under stereomicroscopic control. Force of contraction and contraction times were studied in muscles superfused with medium equilibrated with either 65% xenon and 35% oxygen (xenon group), 1.2% isoflurane in oxygen (isoflurane group), or 65% nitrogen and 35% oxygen (control group). In addition, the positive inotropic effects of calcium, isoproterenol (10(-10)-3 x 10(-8) M) and increasing frequency (0.5-2 Hz) were studied during xenon and isoflurane exposure. Results In contrast to isoflurane, xenon did not alter myocardial force of contraction or contraction times. The positive inotropic effect of isoproterenol, calcium, and increasing pacing frequencies did not differ between the muscles exposed to xenon and the control group. Isoflurane elicited the expected negative inotropic effect (30% reduction of force of contraction) but did not impair the response to inotropic stimuli. Conclusions Xenon does not alter myocardial contractility and the response to inotropic stimuli such as calcium, isoproterenol, or increase in pacing frequency in isolated guinea pig ventricular muscle bundles.

Positive inotropic effects of acetylcholine and BAY K 8644 in embryonic chick ventricle

1987 ◽  
Vol 252 (4) ◽  
pp. H807-H815 ◽  
Author(s):  
Y. Tsuji ◽  
T. Tajima ◽  
J. Yuen ◽  
A. J. Pappano
Keyword(s):  
Action Potentials ◽  
Positive Inotropic Effect ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Phosphoinositide Metabolism ◽  
Ca Channel ◽  
Embryonic Chick ◽  
Muscarinic Agonists ◽  
Cholinergic Agonists ◽  
Inotropic Effects

BAY K 8644 augmented Ca2+-dependent action potentials and evoked a positive inotropic effect in embryonic chick ventricle. These effects are consistent with the properties of this Ca channel "agonist" whose actions are independent of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent phosphorylation. At low to intermediate concentrations (10(-8) to 10(-6) M), the cholinergic agonists acetylcholine, carbachol, and oxotremorine inhibit Ca2+-dependent action potentials and contractions in embryonic ventricle only in the presence of drugs that cause cAMP accumulation. The prediction that low to intermediate concentrations of these cholinergic agonists should not inhibit the effects of BAY K 8644 on Ca2+-dependent action potentials and contractions was borne out experimentally. This result is consistent with the cAMP hypothesis for muscarinic inhibition. It is noteworthy that all cholinergic agonists tested evoked a positive inotropic effect at high concentrations (greater than 10(-6) M) in the presence or absence of BAY K 8644. The positive inotropic effect was initiated by muscarinic receptors for it was blocked by atropine and was independent of endogenous catecholamines, since it occurred in the presence of propranolol. It is speculated that the positive inotropic effect of muscarinic agonists in embryonic heart muscle is related to stimulation of phosphoinositide metabolism.

Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart

1990 ◽  
Vol 259 (4) ◽  
pp. H1239-H1246 ◽  
Author(s):  
M. Karmazyn ◽  
M. P. Moffat
Keyword(s):  
Calcium Channel ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Receptor Interaction ◽  
Inotropic Effects ◽  
Coronary Pressure ◽  
Low Concentrations ◽  
Rat Hearts

We examined the effects of leukotrienes (LT) B4, C4, D4, and E4 (0.010-2.5 ng/ml) on contractile and coronary function in isolated rat hearts. Concentration-dependent effects were examined either by the cumulative addition of LTs or by addition of specific concentrations to individual preparations. Neither LTB4 nor LTE4 produced myocardial or coronary effects at any concentration, irrespective of addition protocol. At 0.010 ng/ml, both LTC4 and LTD4 produced an increase in force that was associated with a 30% elevation in coronary pressure. Further cumulative addition of either leukotriene resulted in a negative inotropic effect and a further increase in coronary pressure. In contrast, following single additions of LTC4 or LTD4 (0.01-0.50 ng/ml) a positive inotropic effect and an increased coronary pressure were observed. LTC4 or LTD4 at 0.5 ng/ml produced a negative inotropic effect in hearts pretreated with 0.01 ng/ml of LTD4 or LTC4, respectively. Reversal of this addition protocol resulted in a negative inotropic effect of either 0.01 ng/ml LTD4 or LTC4. Verapamil and nifedipine significantly attenuated the positive inotropic and coronary constricting effect of 0.5 ng/ml LTC4 and LTD4. The addition of either LT following BAY K 8644 resulted in a negative inotropic effect, in contrast to the positive inotropic influence seen with leukotriene alone. Our results demonstrate a positive inotropic effect of low concentrations of LTC4 and LTD4 concomitant with coronary artery constriction, a phenomenon determined by leukotriene addition protocols and suggestive of LTC4/LTD4 receptor interaction. The effects of calcium channel antagonists and BAY K 8644 on the inotropic response suggest a leukotriene-mediated activation of the calcium channel resulting in increased intracellular calcium concentrations.

Interaction of Halogenated Anesthetics with α- and β-Adrenoceptor Stimulations in Diabetic Rat Myocardium

2004 ◽  
Vol 101 (5) ◽  
pp. 1145-1152 ◽  
Author(s):  
Julien Amour ◽  
Jean-Stéphane David ◽  
Benoît Vivien ◽  
Pierre Coriat ◽  
Bruno Riou
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Positive Inotropic Effect ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Alpha Adrenoceptor ◽  
Positive Inotropic Effects

Background Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. Methods Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD. Results Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. Conclusion Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.

Vasoactive intestinal peptide has a direct positive inotropic effect on isolated human myocardial trabeculae

2001 ◽  
Vol 101 (6) ◽  
pp. 637-643 ◽  
Author(s):  
Ole SAETRUM OPGAARD ◽  
Mikael KNUTSSON ◽  
René DE VRIES ◽  
Beril TOM ◽  
Pramod R. SAXENA ◽  
...  
Keyword(s):  
Left Ventricle ◽  
Vasoactive Intestinal Peptide ◽  
Right Atrium ◽  
Human Heart ◽  
Positive Inotropic Effect ◽  
Contractile Force ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
The Right ◽  
Ventricular Trabeculae

The aim of the present study was to assess the inotropic effects of vasoactive intestinal peptide (VIP) on isolated myocardial trabeculae from the right atrium and the left ventricle of human hearts. Furthermore, using reverse transcriptase-PCR, we wanted to determine the presence of mRNAs encoding the three cloned human VIP receptors, VPAC1, VPAC2 and PAC1. The trabeculae were paced at 1.0Hz in tissue baths, and changes in isometric contractile force upon exposure to agonist were studied. VIP had a potent positive inotropic effect in some of the atrial and ventricular trabeculae tested. This effect was almost completely blocked by the VIP-receptor antagonist VIP-(6-28). mRNAs encoding the human VPAC1, VPAC2 and PAC1 receptors were detected in human myocardial trabeculae from both the right atrium and the left ventricle. In conclusion, VIP has a direct positive inotropic effect in both the atria and the ventricles of the human heart. The presence of mRNAs for the VPAC1, VPAC2 and PAC1 receptors suggest that VIP may mediate its effect via these receptors.

Evidence for physiological functions of protein phosphatases in the heart: evaluation with okadaic acid

1993 ◽  
Vol 265 (1) ◽  
pp. H257-H266 ◽  
Author(s):  
J. Neumann ◽  
P. Boknik ◽  
S. Herzig ◽  
W. Schmitz ◽  
H. Scholz ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Okadaic Acid ◽  
Guinea Pigs ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Force Of Contraction ◽  
Phosphorylation State ◽  
Ventricular Cardiomyocytes ◽  
Channel Currents

Okadaic acid exerts a positive inotropic effect in cardiac preparations. We studied whether the positive inotropic effect of okadaic acid in cardiac preparations could be due to phosphatase inhibition and whether this inhibition affects the phosphorylation of cardiac proteins. In papillary muscles from guinea pigs, 30 microM okadaic acid increased force of contraction to 175% of predrug value. In isolated guinea pig ventricular cardiomyocytes, okadaic acid augmented single Ca(2+)-channel currents by enhancing channel availability. In homogenates from ventricles, 1 microM okadaic acid completely inhibited phosphorylase a phosphatase activity. In isolated 32P-labeled ventricular cardiomyocytes, 30 microM okadaic acid increased phosphorylation of phospholamban (PLB) and troponin inhibitor (TnI) to 325 and 284% of control, respectively. Furthermore, 30 microM okadaic acid increased phosphorylation of a hitherto unknown 23-kDa protein to 352% of control. It is concluded that the effects of okadaic acid could be mediated by increasing the phosphorylation state of several proteins including PLB, a 23-kDa protein, and TnI.

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