Piglet pial arteries respond to N-methyl-D-aspartate in vivo but not in vitro.
Controversy exists concerning whether activation of N-methyl-D-aspartate (NMDA) receptors exerts direct dilator effects on cerebral arteries. The purpose of this study was to examine the responses of isolated piglet arteries to NMDA to determine whether isolated arteries, apart from surrounding neuronal tissue, are capable of responding to NMDA. Piglet arteries (100-200 microm) were isolated from branches of the middle cerebral artery and carefully dissected free of adherent tissue. Arteries were then mounted in an arteriograph system and pressurized to either 30 mm Hg (n=8), 60 mm Hg (n=10), 80 mm Hg (n=6), or 100 mm Hg (n=5). After development of spontaneous tone, NMDA (10(-5) to 10(-3) M) was administered abluminally to the vessels, and no appreciable response was noted (for example; 10(-4) M, 30 mm Hg: 3+/-3% change in active diameter; 60 mm Hg: -4+/-3% change in active diameter). Following a thorough washout, vessels were treated with bradykinin (10(-9) to 10(-7) M), and the arteries did respond (10(-7) M, 30 mm Hg: 26+/-3% change in active diameter; 60 mm Hg: 65+/-10% change in active diameter). In contrast, 10(-5) M and 10(-4) M NMDA dilated arteries in vivo by 9+/-2% and 29+/-6% change in active diameter, respectively (n=6). These results demonstrate that isolated cerebral arteries do not respond directly to NMDA receptor activation. This work confirms our previous in vivo data and is consistent with the hypothesis that cerebral arteries respond to NMDA through a secondary interaction mediated by neuronal release of NO and not to NMDA directly.
Department of Pediatrics, Division of Neonatology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1010, USA. ssimandle@wfubmc.edu
Steve A
SA
Simandle
Brady A
BA
Kerr
Zsombor
Z
Lacza
Delrae M
DM
Eckman
David W
DW
Busija
Ferenc
F
Bari
D000818:Animals; D000831:Animals, Newborn; D001158:Arteries / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D018690:Excitatory Amino Acid Agonists; D014665:Vasodilator Agents; D016202:N-Methylaspartate; D001920:Bradykinin