A hall mark of cardiovascular disease is abnormal neurohumoral activation at the end organ level.This phenotype often exists before these disease states have been established.The mechanism responsible for defective transmission may be related to free radical damage that is secondary to oxidative stress.Soluble guanylate cyclase, the key pre-cursor of cGMP-dependent effects of nitric oxide (NO) is down-regulated in diseased hearts as is the bioavailability of NO itself.