A series of hydrid molecules incorporating the furoxan and nicorandil moieties were designed as potential NO donors with cardiovascular and cerebrovascular activities. Thirty-six target molecules were successfully synthesized by conventional methods and characterized by infrared spactroscopy, ¹H-NMR spectroscopy and highresolution mass spectra. The compounds were tested for their effects on KCl-induced contraction of rabbit thoracic aorta whose endothelium was denuded. Eight compounds were found to reduce KCl-induced contraction by more than 30% at 10μM. All except one of these compounds are characterized by the presence of electron withdrawing groups in the phenyl ring attached via an amide or ester linkage to the furoxan moiety. The nature of the terminal carbonyl linkage (ester or amide) and the length or type of the alkyl chain bridging the two carbonyl functions have little effect on the activity. One of the active compounds, N-(4-methoxy-benzoyl)-N'-[3-methylfuroxanyl-4-carbonyl)piperazine (17i) was tested for hypotensive effects on anaesthesized rats at 1.5mg/kg, and found to demonstrate a gradual and sustained hypotensive effect. The results suggest that the furoxan-nicoradil derivatives are a useful lead in the design of NO-donor compounds for hypertension.