Developmental aspects of endothelial function.

We believe that the mechanisms through which nitric oxide and guanylate cyclase produce relaxation are fully functional in cerebral arteries at term in the fetal sheep and probably also in the term human infant. The relation between cGMP levels and the degree of relaxation varies both with age and with the relaxant used in a vessel specific manner. The factors underlying this variability constitute a fruitful area for future research and include possible age-related changes in membrane potential, calcium channel density and currents, and the participation of cGMP-independent mechanisms, to name only a few. Between fetal and newborn life, the biotransformation of nitroglycerin appears to improve significantly, particularly in the smaller more distal cerebral arteries. This improvement may be a clue to other important vascular metabolic and enzymatic changes that occur during the perinatal period. At the endothelial level, responses to A23187, an index of maximum endothelial vasodilator capacity, are relatively stable across the perinatal period and do not change consistently with age across all arteries. More importantly, large arteries, such as the common carotid, appear to relax better than the smaller cerebral arteries, and this difference is greater in fetal than in adult arteries. Responses to ADP disappear with age in the common carotid, but remain or even become enhanced in the cerebral arteries, thus illustrating the key role played by changes in receptor type and distribution in development and maturation.