Is cyclic GMP a clinically useful marker for ANF action?

The action of ANF is, at least in part, mediated by the activation of particulate guanylate cyclase. Increases in plasma ANF levels induce a marked increase in the plasma levels and urinary excretion of cyclic GMP. In contrast to agents that stimulate particulate guanylate cyclase, activators of soluble guanylate cyclase, such as the bioactive molsidomine metabolite, SIN 1, induce only a modest, not significant, increase in plasma cyclic GMP levels. Thus, increases in plasma cyclic GMP levels appear to be specific for the activation of particulate guanylate cyclase. Cyclic GMP is stable in whole blood in the presence of EDTA and can easily be measured in plasma and urine. It may therefore be a valuable alternative for ANF measurement in the clinical routine. In contrast to urinary ANF excretion, the urinary excretion of cyclic GMP sensitively reflects increases in plasma ANF levels. Measurement of cyclic GMP excretion may therefore be an alternative for plasma ANF and plasma cyclic GMP measurement especially in situations where blood drawing is difficult, e.g. in newborns. Measurement of basal cyclic GMP followed by determination of increases in cyclic GMP levels after injection of a small ANF bolus dose tests the cellular sensitivity to ANF. This may give further insight in the mechanism of the regulation of ANF effects. Therefore, cyclic GMP in many cases appears to be a sensitive marker for the action of ANF in man.