Is measurement of cyclic guanosine monophosphate in plasma or urine suitable for assessing in vivo nitric oxide production?

Abstract

To the Editor: In their recently published article on nitric oxide (NO) synthesis in patients with peripheral arterial occlusive disease Boger et al1 based their conclusions among others on urinary excretion of cyclic guanosine monophosphate (cGMP). The increasing use of urinary and plasma cGMP as a marker of NO production prompts us to critically comment on the basis of doing this. NO stimulates soluble guanylate cyclase and elevates intracellular cGMP.2 The other isoenzyme of guanylate cyclase, particulate guanylate cyclase, is stimulated by natriuretic peptides, which also leads to an increase in intracellular cGMP.3 The induction of cGMP either by natriuretic peptides, NO, or nitrates in target tissues may cause an egression of cGMP into the supernatant.4 5 We observed a release of cGMP into the medium after stimulation of human internal mammary artery grafts with either atrial natriuretic peptide (ANP) or SIN-1 (unpublished results). However, much higher concentrations of SIN-1 were necessary to achieve comparably high cGMP concentrations in the medium. In humans, ANP injections cause a rapid and pronounced increase in plasma and urinary cGMP,6 7 whereas nitroglycerol infusions or molsidomine injections lead to a nonsignificant increase or no increase in peripheral venous plasma cGMP concentrations.6 8 cGMP is only partly eliminated from plasma by glomerular filtration, and most of plasma cGMP is eliminated by extrarenal clearance. Urinary cGMP is primarily of renal cellular origin and correlated with the natriuresis induced by ANP.8 Therefore urinary cGMP has been proposed as a biologic marker for the renal activities of natriuretic peptides in vivo.8 We found no correlation between plasma and urinary cGMP concentrations …