Novel Nitric Oxide Donors Reverse Endothelin-1-Mediated Constriction in Human Blood Vessels: PDF OnlyWiley Katherine E.; Davenport, Anthony P.Journal of Cardiovascular Pharmacology: 2000 - p S151-S152 Free 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-morpholinylsydnonimine (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 useful therapeutic agents in the treatment of cardiovascular disease. Address correspondence and reprint requests to Dr Anthony P. Davenport, Clinical Pharmacology Unit, University of Cambridge, Box 110, Addenbrooke's Hospital, Cambridge, CB2 2QQ, U.K. E-mail: [email protected] © 2000 Lippincott Williams & Wilkins, Inc.