Developmental changes in endothelium-derived vasorelaxant factors in cerebral circulation.
Endothelium-derived prostanoids are predominant vasorelaxant factors in the cerebral circulation of newborn pigs in vivo, whereas in older pigs nitric oxide (NO)-mediated responses also contribute to the regulation of cerebral vascular tone. We compared the expression and activities of NO synthase and cyclooxygenase in the cerebral microcirculation of newborn and adult pigs. In adult animals, expression and activity of endothelial NO synthase in cerebral microvessels and in cultured cerebral endothelial cells is two- to threefold higher than in newborn pigs; acetylcholine and bradykinin cause a greater increase in NO production in adult pigs. Expression and activity of cyclooxygenase in cerebral microvascular endothelial cells is similar in newborn and adult pigs; acetylcholine and bradykinin stimulated dilator prostanoid production to the same degree in both age groups. Endothelial prostanoid synthesis in cerebral microvessels and cultured endothelial cells was inhibited 30-70% by NS-398, reflecting a large contribution of COX-2 in both newborn and adult animals. These data indicate that in the cerebral circulation of pigs, NO synthase is age-dependently upregulated, whereas endothelial cyclooxygenase is not altered during postnatal development.
Parfenova
H
H
Laboratory for Research in Neonatal Physiology, Department of Physiology, University of Tennessee, Memphis, Tennessee 38163, USA.
Massie
V
V
Leffler
C W
CW
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging; D000818:Animals; D000831:Animals, Newborn; D001920:Bradykinin / Q000494:pharmacology; D001921:Brain / Q000098:blood supply*; D002478:Cells, Cultured; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000254:growth & development* / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D008833:Microcirculation / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D013552:Swine; D014665:Vasodilator Agents / Q000097:blood*
D007527:Isoenzymes; D011453:Prostaglandins; D014665:Vasodilator Agents; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone; D000109:Acetylcholine; D001920:Bradykinin