Age-dependent mechanisms of cerebrovascular regulation in the pig

Many newborn piglet cerebrovascular responses are mediated by prostanoids, with little, if any contribution from nitric oxide (NO). Furthermore, the mechanism of action of prostanoids appears to be permissive in nature. However, certain juvenile pig cerebrovascular responses require both prostanoids and NO for complete responses to occur. Whether prostanoids and/or NO act directly or permissively in the juvenile cerebral circulation is not known.; Studies were designed to test the hypothesis that during development from newborn to juvenile, the mechanisms of cerebrovascular regulation are altered, such that the predominant EDRF that provides a permissive signal to the underlying smooth muscle changes from a primarily prostanoid-dependent to a primarily NO-dependent mechanism.; Newborn and juvenile pigs were implanted with closed cranial windows to determine age-related requirements for prostanoid and NO in pial arteriolar responses to hypercapnia, histamine, and bradykinin, as well as NO and prostanoid mechanisms of action. The light/dye endothelial injury technique was utilized to determine endothelial-dependency of newborn and juvenile pig pial arteriolar responses. Additional studies were performed using cerebral microvascular endothelial cells isolated from newborn and juvenile pig brain for determination of NO production.; Newborn pial arteriolar responses to hypercapnia, histamine and bradykinin were sensitive to cyclooxygenase (COX), but not NO synthase (NOS) inhibition. Juvenile pial arteriolar responses to hypercapnia and bradykinin were attenuated when either COX or NOS was inhibited. Newborn and juvenile responses to hypercapnia and bradykinin were endothelium-dependent. Acetylcholine-induced constriction in both age groups was not dependent on a functional endothelium, whereas juvenile dilatory responses to acetylcholine were endothelium-dependent. In newborns, prostanoids but not NO can act permissively to cause dilation in response to hypercapnia, histamine, and bradykinin. Juvenile hypercapnic, bradykinin, and acetylcholine responses can involve NO acting in a permissive capacity. Juvenile, but not newborn cerebral microvascular endothelial cells in primary culture produce detectable amounts of NO when stimulated with acetylcholine or ionomycin.; In conclusion, these data suggest that during development from newborn to juvenile, the mechanisms of cerebrovascular regulation are altered, such that the predominant EDRF providing a permissive signal to the underlying smooth muscle changes from a primarily prostanoid-dependent to a primarily NO-dependent mechanism.