Nitric Oxide Synthesis/Pathway Inhibitors in Daphnia magna Reverse Alcohol-Induced Heart Rate Decrease

(1) Central Bucks East High School, Doylestown, Pennsylvania, (2) Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, (3) Janssen Pharmaceuticals, Malvern, Pennsylvania

https://doi.org/10.59720/19-050
Cover photo for Nitric Oxide Synthesis/Pathway Inhibitors in Daphnia magna Reverse Alcohol-Induced Heart Rate Decrease

Studies show that alcohol causes oxidative stress and heart rate (HR) depression in humans. Chronic alcohol consumption also causes cardiac myopathy, which afflicts about 500,000 Americans annually. The present study aims to understand how alcohol reduces HR and examine if select chemical agents with inhibitory effects on nitric oxide levels can reverse the effects of alcohol on HR. In this study, we used Daphnia magna, a water crustacean with a large and a transparent heart, as an in vitro model to study the effects of agents such as methylene blue (a guanylyl cyclase inhibitor), melatonin (a free radical scavenger and Phosphodiesterase E5 (PDE5) inhibitor), L-glutamate (N-methyl-D-Aspartate (NMDA)-ion channel stimulator), and L-N(gamma)-nitroarginine methyl ester (L-NAME, nitric oxide synthase inhibitor) on HR by alcohol. We also examined the ability of these agents to prevent a decrease in the HR by alcohol by changing the order in which we exposed the Daphnia to the substances. Alcohol exposure decreased HR by 27% after 30 minutes of exposure. The experiment measured the ability of various drugs to reverse this decrease in HR. Methylene blue, after 10 minutes of exposure, increased the HR by 15%. Melatonin, after 10 minutes exposure, increased the HR by 27%. Similarly, L-NAME and L-glutamate, after 10 minutes of exposure, increased the HR by 20% and 36%, respectively. These results showed that alcohol’s depressive effects on HR could be mediated through nitric oxide generation and confirmed the hypothesis that nitric oxide synthesis inhibitors can reverse alcohol-induced HR decrease in Daphnia magna.

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