Endothelial NO and prostanoid involvement in newborn and juvenile pig pial arteriolar vasomotor responses.
Specific cerebrovascular dilatory responses in newborn piglets are entirely prostanoid dependent, but require both nitric oxide (NO) and prostanoids in juveniles. We examined endothelial dependency and mechanisms of NO- and prostanoid-mediated cerebrovascular responses in anesthetized newborn and juvenile pigs implanted with closed cranial windows. Light/dye endothelial injury inhibited newborn and juvenile hypercapnic and bradykinin (BK) responses and inhibited dilation to acetylcholine in juveniles. Iloprost and NO act permissively in restoring light/dye inhibited newborn and juvenile responses, respectively. Differences in sensitivity to iloprost and sodium nitroprusside were not observed. Juvenile (not newborn) hypercapnic and BK cerebrovascular responses were sensitive to soluble guanylyl cyclase inhibition. Pial arteriolar diameter and cortical production of prostacyclin, cAMP, and cGMP in response to BK were measured under control conditions, after treatment with indomethacin and/or N(omega)-nitro-L-arginine methyl ester (L-NAME). Indomethacin inhibited BK responses in newborns. Juvenile responses were inhibited by L-NAME, and mildly by indomethacin. Cortical 6-keto-PGF(1 alpha), cAMP, and cGMP increased in response to BK in both age groups. Newborn cerebrovascular responses are largely NO independent, but NO becomes more important with maturation.
Willis
A P
AP
Laboratory for Research in Neonatal Physiology, Department of Physiology, The University of Tennessee Health Science Center, Memphis, 38163, USA.
Leffler
C W
CW
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000109:Acetylcholine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000378:metabolism; D001920:Bradykinin / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000502:physiology*; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004730:Endothelium, Vascular / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000378:metabolism; D005260:Female; D006935:Hypercapnia / Q000378:metabolism; D016285:Iloprost / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D002317:Cardiovascular Agents; D004791:Enzyme Inhibitors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D016285:Iloprost; D007545:Isoproterenol; D000109:Acetylcholine; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin