Relationship between systemic nitric oxide metabolites and cyclic GMP in healthy male volunteers

Aim: Nitric oxide (NO) is an endogenous mediator of many physiological processes, many of which are mediated by cyclic guanosine 3′,5′‐monophosphate (cGMP). Much effort has been made to validate clinical markers of NO production or bioavailability. While the measurement of plasma nitrate, nitrite, and cGMP concentrations have been suggested to reflect endogenous production of NO, there is no study showing whether there is correlation between these three markers. In the present study, we investigate whether there is correlation between the plasma concentrations of nitrate, nitrite, and cGMP in a relatively homogeneous group of 141 healthy subjects. Methods: Venous blood samples were collected from healthy male subjects and plasma aliquots were then immediately removed and stored at ?70 °C until analysed in duplicate for their nitrite and nitrate content using ozone‐based chemiluminescence assays. Plasma cGMP levels were determined by using a commercial enzyme immunoassay. Results: While we found no significant correlation between plasma nitrite and nitrate concentrations (P = 0.747), or between plasma nitrate and cGMP concentrations (P = 0.221), a significant positive correlation was found between plasma cGMP and nitrite concentrations (P = 0.017, r_s = 0.270). Conclusions: The significant correlation we found between plasma nitrite and cGMP concentrations is consistent with the notion that nitrite or cGMP concentrations in plasma may be useful clinical markers of NO formation in healthy subjects.