Effects of maturation on cyclic GMP metabolism in ovine carotid arteries.

Abstract

Previous studies suggest that elevated basal levels of cGMP in newborn arteries may help explain why vascular resistance is lower in newborns than adults. To explore the reasons why basal cGMP is higher in neonatal arteries, the present studies examined rates of cGMP synthesis and degradation in newborn and adult ovine common carotid arteries. The measurements were performed in both intact and homogenized arteries, and results were normalized relative to cell water to estimate intracellular concentrations and minimize errors due to compositional differences between newborn and adult arteries. Steady state levels of cGMP measured under baseline conditions averaged 0.11 +/- 0.02 microM in adult arteries and 0.59 +/- 0.11 microM in newborn arteries. These resting cGMP levels were unaffected by endothelium removal. Under baseline conditions, steady state rates of cGMP synthesis (mumol of cGMP/L of cell water/min) were higher in newborn (0.31 +/- 0.06) than in adult (0.15 +/- 0.04) arteries. Maximal rates of cGMP degradation (mumol of cGMP/L of cell water/min) measured in artery homogenates were also much higher in preparations of newborn (106 +/- 6) than of adult (78 +/- 6) arteries. Together, these data suggest that the reason resting cGMP concentrations were higher in newborn than in adult arteries was due at least in part to a higher basal rate of cGMP synthesis in the newborn. Estimates of apparent Km values for PDE were also greater in newborn (2.9 microM) than in adult (1.5 microM) preparations, suggesting that age-related differences in the Km for PDE may also contribute to the elevated basal concentration of cGMP observed in the newborn.