Perinatal vascular development
Authors: R Higgins
Journal: Cardiovascular Research (2001)

See article by Boels et al. [3] ( pages 140 -150) in thisdisorders.Physiology of the pulmonary vascular bed and issue.influences of vasodilators, such as bradykinin, acetylcholine and substance P, change dramatically in the piglet During transition to the extrauterine environment, the pulmonary artery model used in this study.In the fetus, newborn infant must accomplish complex cardiorespiratory bradykinin-mediated relaxation is completely dependent on adjustments.Dramatic changes in pulmonary and systemic the local release of nitric oxide.In the immediate postnatal vascular resistance must occur within minutes, followed by period, bradykinin relaxation evolves to depend on prostamore gradual changes over the succeeding days.A host of glandin synthesis, in addition to nitric oxide synthesis.This mediators of vascular tone are involved in these processes is in contrast to other endothelium-dependent vasodilators and these have been the focus of extensive study.Differen-including acetylcholine and substance P. In the adult tial responses from different vascular beds contribute to endothelium, bradykinin-dependent relaxation becomes these circulatory changes; a variety of exogenous and almost completely independent of nitric oxide.endogenous factors affect the responsiveness of vascular Persistent pulmonary hypertension causes significant beds to vasoactive mediators.When these critical circulat-morbidity and mortality in the newborn infant.Current ory changes are not accomplished successfully, the life-treatment consists of respiratory support with mechanical threatening disorder known as persistent pulmonary hy-ventilation, including conventional and high frequency pertension of the newborn may result [1].In older subjects, modalities, blood pressure maintenance, including the use pulmonary hypertension associated with the acute respira-of inotrophic agents and volume expansion, vasodilators tory distress syndrome, congenital heart disease with left-and extracorporeal membrane oxygenation (ECMO).to-right shunt, and primary pulmonary hypertension remain Clearly, these therapies themselves can have significant baffling challenges for the clinician.At the same time, complications.The use of inhaled nitric oxide (iNO) as a excessive vasodilatation mediated by increased endogen-selective pulmonary vasodilator has recently become wideous production of nitric oxide has been implicated in the ly available.Its effectiveness is well documented in several pathogenesis of septic shock [2].Thus, modulation of randomized clinical trials [4,5].iNO, along with adjuvant vascular tone is a critical homeostatic mechanism whose therapies such as high frequency ventilation has clearly failure can lead to life-threatening derangements; it is a reduced the need for ECMO, but not all infants respond subject well worth of the extensive research attention it has well to the drug.In some instances, the failure to respond received.may be related to inadequate aeration of the lungs or other Boels et al. describe a developmental assessment of the factors.However, it is evident from a variety of clinical mechanisms of bradykinin-induced relaxations in pulmon-studies that infants with certain conditions, such as sepsis ary arteries in this issue of Cardiovascular Research [3].or congenital diaphragmatic hernia, respond less well to This represents an important contribution, because im-iNO even when the drug is administered optimally [6].proved understanding of the mechanisms of pulmonary Furthermore, the therapeutic benefit of iNO appears to be vascular bed reactivity and the developmentally deter-much less dramatic in older children and adults with only mined characteristics are vitally important to developing modest improvement in oxygenation without improvement potential strategies for the treatment of pulmonary vascular in survival [7].Boels et al. [3] demonstrate that the size and location (large vs. small arteries) of the blood vessels markedly influence the effects of vasodilating agents