Effects of compound 48/80 on the guinea-pig isolated heart: A comparison with the in vitro cardiac anaphylaxis

Gomes, J.C.; Antonio, A.

doi:10.1016/s0031-6989(81)80047-1

Cited by 7 publications

(3 citation statements)

References 13 publications

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“…We present tentative evidence that histamine can be released from the H 2 -TG atrium, as compound 48/80 exerts a cimetidine sensitive effect ( Figure 4 ). It is well known that compound 48/80 can extrude histamine from the heart (guinea pig heart: Gomez and Antonio, 1981 ; human heart: Patella et al, 1995 ). Unfortunately, it is currently unclear from which cell type histamine is released in H 2 -TG atrium by compound 48/80.…”

Section: Discussionmentioning

confidence: 99%

Histamine can be Formed and Degraded in the Human and Mouse Heart

et al. 2021

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Histamine is metabolized by several enzymes in vitro and in vivo. The relevance of this metabolism in the mammalian heart in vivo is unclear. However, histamine can exert positive inotropic effects (PIE) and positive chronotropic effects (PCE) in humans via H2-histamine receptors. In transgenic mice (H2-TG) that overexpress the human H2 receptor in cardiomyocytes but not in wild-type littermate mice (WT), histamine induced PIE and PCE in isolated left or right atrial preparations. These H2-TG were used to investigate the putative relevance of histamine degrading enzymes in the mammalian heart. Histidine, the precursor of histamine, increased force of contraction (FOC) in human atrial preparations. Moreover, histamine increased the phosphorylation state of phospholamban in human atrium. Here, we could detect histidine decarboxylase (HDC) and histamine itself in cardiomyocytes of mouse hearts. Moreover, our data indicate that histamine is subject to degradation in the mammalian heart. Inhibition of the histamine metabolizing enzymes diamine oxidase (DAO) and monoamine oxidase (MAO) shifted the concentration response curves for the PIE in H2-TG atria to the left. Moreover, activity of histamine metabolizing enzymes was present in mouse cardiac samples as well as in human atrial samples. Thus, drugs used for other indication (e.g. antidepressants) can alter histamine levels in the heart. Our results deepen our understanding of the physiological role of histamine in the mouse and human heart. Our findings might be clinically relevant because we show enzyme targets for drugs to modify the beating rate and force of the human heart.

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Section: Discussionmentioning

confidence: 99%

Histamine can be Formed and Degraded in the Human and Mouse Heart

et al. 2021

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“…Shock was induced with C48/80 (3 mg/kg) by intravenous bolus injection, 5 min before (prophylactic) or after (treatment) the administration of the inhibitors [MB (3 mg/kg), L-NAME (1 mg/kg), IC (3 mg/kg)]. The doses for the drugs were chosen based on literature data (9,(18)(19)(20).…”

Section: Experimental Design and Treatment Protocolmentioning

confidence: 99%

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Albuquerque

Ferreira

Carvalho

et al. 2020

Braz J Med Biol Res

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Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), N o-nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

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Section: Experimental Design and Treatment Protocolmentioning

confidence: 99%

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

et al. 2013

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Anaphylactic shock can be defined as an acute syndrome, and it is the most severe clinical manifestation of allergic diseases. Anaphylactoid reactions are similar to anaphylactic events but differ in the pathophysiological mechanism. Nitric oxide (NO) inhibitors during anaphylaxis suggest that NO might decrease the signs and symptoms of anaphylaxis but exacerbate associated vasodilation. Therefore, blocking the effects of NO on vascular smooth muscle by inhibiting the guanylate cyclase (GC) would be a reasonable strategy. This study aimed to investigate the effects of NO/cGMP pathway inhibitors methylene blue (MB), N o -nitro-L-arginine methyl ester hydrochloride (L-NAME), and indigo carmine (IC) in shock induced by compound 48/80 (C48/80) in rats. The effect was assessed by invasive blood pressure measurement. Shock was initiated by C48/80 intravenous bolus injection 5 min before (prophylactic) or after (treatment) the administration of the inhibitors MB (3 mg/kg), L-NAME (1 mg/kg), and IC (3 mg/kg). Of the groups that received drugs as prophylaxis for shock, only the IC group did not present the final systolic blood pressure (SBP) better than the C48/80 group. Regarding shock treatment with the drugs tested, all groups had the final SBP similar to the C48/80group. Altogether, our results suggested that inhibition of GC and NO synthase in NO production pathway was not sufficient to revert hypotension or significantly improve survival.

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Effects of compound 48/80 on the guinea-pig isolated heart: A comparison with the in vitro cardiac anaphylaxis

Cited by 7 publications

References 13 publications

Histamine can be Formed and Degraded in the Human and Mouse Heart

Histamine can be Formed and Degraded in the Human and Mouse Heart

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

Effects of NO/cGMP inhibitors in a rat model of anaphylactoid shock

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