however, experimental studies need to be performed in order to confirm this directionality, especially considering the volume of experimental data that supports an effect of H2S onNO, as well as an effect of NO on H2S. Thus, we present here a theoretical model, supported by our human observational studies, for the regulation of microvascular tone in the preterm newborn by the action and interaction of the gasotransmitters, which provides a construct from which future experimental studies may work in order to understand the development of circulatory compromise in this vulnerable population. The inhibition of CSE prevents the increased H2S production observed at 24h postnatal age in the preterm guinea pig pup, and CSE-dependent, but not CSE-independent H2S production is associated with increased microvascular blood flow. The relationship between NO and CSE/H2S needs to be investigated further, particularly as this appears to be associated with higher microvascular blood flow as measured by laser Doppler. Contrary to our previous findings, we observed a significant, positive relationship between NO and microvascular blood flow at 24h postnatal age in male neonates. One source of these differing results may be the use of different methodology��in our previous papers NO metabolites were standardised to creatinine to allow for comparisons between time points and subjects. It has been shown, however, that creatinine may not be the best molecule for this purpose in the neonate as levels change significantly in the transitional period. In females, a lower contribution of H2S to microvascular tone regulation was predicted when the other gasotransmitters were added into the model. This suggests that the effect of either NO, CO, or both, negates the effect of H2S to such a degree that there is no net effect on vascular tone. This may be primarily due to CO, which is inversely correlated with H2S and may reflect an inhibitory action of CO on H2S, in line with published reports that have demonstrated that CO decreases the production and action of H2S. This is of particular interest in this JNJ 10191584 maleate cohort, as females and males had comparable levels of CO, suggesting some protective role of this molecule against inappropriate vasodilation in the female. The JNJ DGAT2-A findings of our current study are discrepant with our previous studies, which showed that males had higher levels of CO and that this was associated with inappropriate peripheral microvascular dilatation and physiological instability in the first few days of life. There are a number of possible explanations for these differences.