Determinants of the response of human blood vessels to nitric oxide donorsin vivo

The potency of the nitric oxide (NO) donors glyceryltrinitrate (GTN) and 3- morpholinosydnonimine was compared in human dorsal hand veins, the radial a rtery, and the forearm resistance vessels. NO donors were more potent in ve ins and the radial artery (vessels with minimal basal NO-mediated dilatatio n) than in the resistance vascular bed (where basal NO is a major determina nt of vascular tone). In contrast, 8-bromoguanosine 3',5'-cyclic monophosph ate (a cGMP mimetic) was approximately equipotent in resistance arteries an d veins and was less potent in the radial artery. Inhibition of phosphodies terase V with dipyridamole did not alter the arteriovenous profile of GTN. Increasing the local concentration of NO in veins (by infusing sodium nitro prusside) reduced their sensitivity to GTN but not to 8-bromoguanosine 3',5 '-cyclic monophosphate. Conversely, reducing endogenous NO production in th e resistance vasculature led to time-dependent increases in the response to GTN. These data suggest that soluble guanylate cyclase rather than cGMP-de pendent protein kinase or phosphodiesterase V is the site in the second mes senger pathway that determines the arteriovenous profile of NO donors. More over, the sensitivity of soluble guanylate cyclase to NO donors might be re gulated by the ambient concentration of NO, with increased local NO down-re gulating the dilator response to NO donors.