Novel nitric oxide donors reverse endothelin-1-mediated constriction in human blood vessels

Cardiovascular disease is associated with elevated circulating plasma level s of endothelin-1 (ET-1). Our aim was to compare the ability of the nitric oxide donors (NO-donors) 5-morpholinyl-sydnonimine (SIN-1) and S-nitroso-N- acetylpenicillamine (SNAP) with the novel nitric oxide donors (NONOates) di ethylamine NONOate (DEA/NO), and diethylenetriamine NONOate (DETA/NO) in or der to physiologically antagonize ET-1-mediated constriction of human inter nal mammary arteries (IMA) in vitro. Both SNAP and DETA/NO caused a signifi cant rightward shift in the ET-1 concentration-response curve. All four NO- donors were found to completely reverse an established contraction to a sub maximal 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 FT-1 in human arteries and ma y prove to be useful therapeutic agents in the treatment of cardiovascular disease.