Functional Consequences of Endothelial NO Formation

Following its synthesis NO, both in endothelial cells and in the adjacent smooth muscle cells, activates what has been termed its intracellular receptor, soluble guanylate cyclase. NO binds to the heme iron in the catalytic domain of the enzyme and by increasing its activity leads to an enhanced formation of cGMP (Drexler et al., 1989 Martin et al., 

Activation of K ca channels following application of NO or NO donors has also been reported to be mimicked by an activator of the cGMP-dependent protein kinase (Archer et al., 1994), suggesting that the pathway linking NO with K ca channel activation is cGMP dependent. 

NO is not simply a vasodilator, since, in different preparations of cardiac muscle, endothelium-derived NO as well as NO donors and cGMP analogs appear to enhance myocardial relaxation, decrease diastolic tone, and slightly reduce peak contraction (Shah et al., 1994). The subcellular mechanism of these effects is proposed to be a cGMP-induced reduction in the myofilament response to Ca (Shah etal., 1994). NO-mediated endogenous 

---