ET-1 contributes to age-dependent G protein impairment after brain injury.
Previous studies have observed that endothelin-1 (ET-1) concentration is elevated in CSF and contributes to impaired cerebral hemodynamics following fluid percussion brain injury (FPI) in an age-dependent manner. This study was designed to characterize the effects of FPI on the vascular activity of two activators of a pertussin toxin-sensitive G protein, mastoparan and mastoparan-7, as a function of age and the role of ET-1 in such effects in newborn (1-5 days old) and juvenile (3-4 weeks old) pigs equipped with a closed cranial window. Mastoparan (10(-8), 10(-6) M) elicited pial artery dilation that was blunted more by FPI in newborn versus juvenile pigs (9 +/- 1 and 16 +/- 1 vs. 3 +/- 1 and 5 +/- 1%, newborn; 9 +/- 1 and 15 +/- 1 vs. 6 +/- 1 and 9 +/- 1%, juvenile). Similar results were observed for mastoparan-7, but the inactive analogue mastoparan-17 had no effect on pial diameter. BQ123 (10(-6) M), an ET-1 antagonist, partially restored impaired mastoparan dilation after FPI in the newborn but not in the juvenile (3 +/- 1 and 5 +/- 1 vs. 7 +/- 1 and 11 +/- 1%, newborn; 6 +/- 1 and 9 +/- 1 vs. 6 +/- 1 and 10 +/- 1%, juvenile). These data show that G protein activation elicits cerebrovasodilation that is blunted following FPI in an age-dependent manner. These data suggest that ET-1 contributes to the impairment of G protein-mediated vasodilation in an age-dependent manner after FPI.
Armstead
William M
WM
Departments of Anesthesia and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. armstead@mail.med.upenn.edu
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000134:cerebrospinal fluid*; D002245:Carbon Dioxide / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1 / Q000134:cerebrospinal fluid*; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D010100:Oxygen / Q000097:blood; D010455:Peptides; D037342:Pertussis Toxin / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014862:Wasp Venoms / Q000494:pharmacology
D019332:Endothelin-1; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D002245:Carbon Dioxide; C037500:mastoparan; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D010100:Oxygen