Vasorelaxant Effect of Novel Nitric Oxide-Hydrogen Sulfide Donor Chalcone in Isolated Rat Aorta: Involvement of cGMP Mediated sGC and Potassium Channel Activation

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Author(s): Amol Sherikar*, Rakesh Dhavale, Manish Bhatia.

Journal Name: Current Molecular Pharmacology

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Background and Objective: Recently nitric oxide (NO) and hydrogen sulfide (H2S) donating moieties were extensively studied for their role in the vasculature as they are responsible for many cellular and pathophysiological functioning. The objective of the present study is to evaluate novel NO and H2S donating chalcone moieties on isolated rat aorta for vasorelaxation, and to investigate the probable mechanism of action.

Methods: To extend our knowledge of vasorelaxation by NO and H2S donor drugs, here we have investigated the vasorelaxing activity of novel NO and H2S donating chalcone moieties on isolated rat aorta. The mechanism of vasorelaxation by these molecules was investigated by performing in-vitro cGMP mediated sGC activation assay and using Tetraethylammonium chloride (TEA) as a potassium channel blocker, and Methylene blue as NO blocker.

Results: Both NO and H2S donating chalcone moieties were found to be potent vasorelaxant. The compound G4 and G5 produce the highest vasorelaxation with 3.716 and 3.789 M of pEC50 respectively. After the addition of TEA, G4 and G5 showed 2.772 and 2.796 M of pEC50 respectively. The compound Ca1, Ca2, and D7 produced significant activation and release of cGMP mediated sGC which was 1.677, 1.769 and 1.768 M of pEC50 respectively.

Conclusion: The vasorelaxation by NO-donating chalcones was blocked by Methylene blue but it did not show any effect on H2S donating chalcones. The vasorelaxing potency of NO-donating molecules was observed to be less affected by the addition of TEA but H2S donors showed a decrease in both efficacy and potency. The cGMP release was more in case of NO-donating molecules. The tested compounds were found potent for relaxing vasculature of rat aorta.

Keywords: Vasorelaxation, Nitric oxide, Hydrogen sulfide, Tetraethylammonium chloride (TEA), In-vitro, cGMP mediated sGC

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(E-pub Ahead of Print)
DOI: 10.2174/1874467212666191025092346
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