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3,4-Methylenedioxymethamphetamine alters left ventricular function and activates nuclear factor-Kappa B (NF-κB) in a time and dose dependent manner.

Tiangco DA, Halcomb S, Lattanzio FA, Hargrave BY - Int J Mol Sci (2010)

Bottom Line: 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described.We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2).The current results suggest that MDMA is acutely detrimental to heart function and that an intact cardiovascular NOS system is important to help mitigate early sequelae in some functional parameters.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.

ABSTRACT
3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described. In the current study, we observed the effects of acute MDMA on rabbit left ventricular function. We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2). In the rabbit, MDMA (2 mg/kg) alone caused a significant increase in heart rate and a significant decrease in the duration of the cardiac cycle. Inhibition of nitric oxide synthase (NOS) by pretreatment with L-NAME (10 mg/kg) alone caused significant dysfunction in heart rate, systolic pressure, diastolic pressure, duration of relaxation, duration of cardiac cycle, and mean left ventricular pressure. Pretreatment with L-NAME followed by treatment with MDMA caused significant dysfunction in additional parameters that were not abnormal upon exposure to either compound in isolation: duration of contraction, inotropy, and pulse pressure. Exposure to 1.0 mM MDMA for 6 h or 2.0 μM MDMA for 12 h caused increased nuclear localization of NF-κB in cultured H9c2 cells. The current results suggest that MDMA is acutely detrimental to heart function and that an intact cardiovascular NOS system is important to help mitigate early sequelae in some functional parameters. The delayed timing of NF-κB activation suggests that this factor may be relevant to MDMA induced cardiomyopathy of later onset.

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Effects of L-NAME on cardiac functional parameters (mean ± SD). L-NAME + MDMA group (n = 4). Pre-injection parameters were record for 15 minutes. Post-injection of 10 mg/kg L-NAME was recorded for 10 minutes. * p < 0.05 compared to pre-injection.
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f10-ijms-11-04843: Effects of L-NAME on cardiac functional parameters (mean ± SD). L-NAME + MDMA group (n = 4). Pre-injection parameters were record for 15 minutes. Post-injection of 10 mg/kg L-NAME was recorded for 10 minutes. * p < 0.05 compared to pre-injection.

Mentions: L-NAME alone significantly decreased heart rate, but elevated systolic pressure, diastolic pressure, duration of relaxation, duration of cardiac cycle, and mean pressure (Figure 10). DCON, dP/dt, and PulseP were not significantly affected by L-NAME alone. However, after the addition of MDMA, these parameters were significantly increased.


3,4-Methylenedioxymethamphetamine alters left ventricular function and activates nuclear factor-Kappa B (NF-κB) in a time and dose dependent manner.

Tiangco DA, Halcomb S, Lattanzio FA, Hargrave BY - Int J Mol Sci (2010)

Effects of L-NAME on cardiac functional parameters (mean ± SD). L-NAME + MDMA group (n = 4). Pre-injection parameters were record for 15 minutes. Post-injection of 10 mg/kg L-NAME was recorded for 10 minutes. * p < 0.05 compared to pre-injection.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3100831&req=5

f10-ijms-11-04843: Effects of L-NAME on cardiac functional parameters (mean ± SD). L-NAME + MDMA group (n = 4). Pre-injection parameters were record for 15 minutes. Post-injection of 10 mg/kg L-NAME was recorded for 10 minutes. * p < 0.05 compared to pre-injection.
Mentions: L-NAME alone significantly decreased heart rate, but elevated systolic pressure, diastolic pressure, duration of relaxation, duration of cardiac cycle, and mean pressure (Figure 10). DCON, dP/dt, and PulseP were not significantly affected by L-NAME alone. However, after the addition of MDMA, these parameters were significantly increased.

Bottom Line: 3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described.We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2).The current results suggest that MDMA is acutely detrimental to heart function and that an intact cardiovascular NOS system is important to help mitigate early sequelae in some functional parameters.

View Article: PubMed Central - PubMed

Affiliation: Department of Biological Sciences, Old Dominion University, Norfolk, VA 23529, USA.

ABSTRACT
3,4-Methylenedioxymethamphetamine (MDMA) is an illicit psychoactive drug with cardiovascular effects that have not been fully described. In the current study, we observed the effects of acute MDMA on rabbit left ventricular function. We also observed the effects of MDMA on nuclear factor-kappa B (NF-κB) activity in cultured rat ventricular myocytes (H9c2). In the rabbit, MDMA (2 mg/kg) alone caused a significant increase in heart rate and a significant decrease in the duration of the cardiac cycle. Inhibition of nitric oxide synthase (NOS) by pretreatment with L-NAME (10 mg/kg) alone caused significant dysfunction in heart rate, systolic pressure, diastolic pressure, duration of relaxation, duration of cardiac cycle, and mean left ventricular pressure. Pretreatment with L-NAME followed by treatment with MDMA caused significant dysfunction in additional parameters that were not abnormal upon exposure to either compound in isolation: duration of contraction, inotropy, and pulse pressure. Exposure to 1.0 mM MDMA for 6 h or 2.0 μM MDMA for 12 h caused increased nuclear localization of NF-κB in cultured H9c2 cells. The current results suggest that MDMA is acutely detrimental to heart function and that an intact cardiovascular NOS system is important to help mitigate early sequelae in some functional parameters. The delayed timing of NF-κB activation suggests that this factor may be relevant to MDMA induced cardiomyopathy of later onset.

Show MeSH
Related in: MedlinePlus