Novel Nitric Oxide Donors Reverse Endothelin-1-Mediated Constriction in Human Blood Vessels

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Abstract
Summary: Cardiovascular disease is associated with elevated circulating plasma levels of endothelin-1 (ET-1). Our aim was to compare the ability of the nitric oxide donors (NO-donors) 3-morpholinyl-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP) with the novel nitric oxide donors (NONOates) diethylamine NONOate (DEA/NO), and diethylenetriamine NONOate (DETA/NO) in order to physiologically antagonize ET-1-mediated constriction of human internal mammary arteries (IMA) in vitro. Both SNAP and DETA/NO caused a significant rightward shift in the ET-1 concentration-response curve. All four NO-donors were found to completely reverse an established contraction to a submaximal concentration of ET-1 (decreasing order of potency; SNAP> DEA/NO > SIN-1 > DETA/NO). These data suggest that the NONOates DEA/NO and DETA/NO can physiologically antagonize the effects of ET-1 in human arteries and may prove to be use-ful therapeutic agents in the treatment of cardiovascular disease.

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