Novel nitric oxide donors reverse endothelin-1-mediated constriction in human blood vessels.
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 ET-1 (decreasing order 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.
Wiley
K E
KE
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, UK.
Davenport
A P
AP
D000368:Aged; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008323:Mammary Arteries / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D019332:Endothelin-1; D020030:Nitric Oxide Donors