title: Role of endothelin-1 in age-dependent cerebrovascular hypotensive responses after brain injury.
abstract: This study was designed to compare the effect of fluid percussion brain injury (FPI) on the hypotensive cerebrovascular response in newborn and juvenile pigs as a function of time postinsult and to determine the role of endothelin-1 (ET-1) in any age-dependent differences in hypotensive cerebrovascular regulation after injury. Ten minutes of hypotension (10-15 ml blood/kg) decreased mean arterial blood pressure uniformly in both groups ( approximately 45%). In the newborn, hypotensive pial artery dilation (PAD) was blunted within 1 h, remained diminished for at least 72 h, but was resolved within 168 h postinjury (66 +/- 4, 69 +/- 4, 71 +/- 4, and 64 +/- 4% inhibition at 1, 4, 8, and 72 h post-FPI). During normotension, regional cerebral blood flow (rCBF) was decreased by FPI, and hypotension further reduced the already decremented rCBF for at least 72 h. Cerebrospinal fluid (CSF) ET-1 was increased from 26 +/- 4 to 206 +/- 25 pg/ml within 72 h post-FPI, whereas an ET-1 antagonist partially restored impaired hypotensive PAD and altered hypotensive rCBF. In contrast, hypotensive PAD and altered CBF were only inhibited for 4 h post-FPI in the juvenile (56 +/- 3 and 34 +/- 4% inhibition at 1 and 4 h post-FPI). CSF ET-1 was only increased from 27 +/- 4 to 67 +/- 9 pg/ml at 4 h, whereas the concentration returned to preinjury value by 8 h post-FPI. ET-1 antagonism similarly partially restored impaired hypotensive PAD and altered hypotensive rCBF. These data show that FPI disturbs cerebral autoregulation during hypotension both to a greater magnitude and for a longer duration in the newborn than in the juvenile. These data suggest that the greater FPI-induced ET-1 release in the newborn could contribute to age-dependent differences in impaired hypotensive cerebral autoregulation after FPI.
authors.affiliation: Department of Anesthesia, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Armstead
mesh_terms: D000375:Aging / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000502:physiology; D001158:Arteries / Q000503:physiopathology; D001794:Blood Pressure; D001930:Brain Injuries / Q000150:complications*; D002560:Cerebrovascular Circulation; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006706:Homeostasis; D007022:Hypotension / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D013997:Time Factors; D014664:Vasodilation; D014949:Wounds, Nonpenetrating / Q000150:complications*
chemical_list: D019332:Endothelin-1