N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets.
N-methyl-D-aspartate (NMDA) elicits pial arteriolar dilation that has been associated with neuronal nitric oxide (NO) production. However, endothelial factors or glial P-450 epoxygenase products may play a role. We tested whether NMDA-induced pial vasodilation 1) primarily involves NO diffusion from the parenchyma to the surface arterioles, 2) involves intact endothelial function, and 3) involves a miconazole-sensitive component. Arteriolar diameters were determined using closed cranial window-intravital microscopy in anesthetized piglets. NMDA (10-100 microM) elicited virtually identical dose-dependent dilations in paired arterioles (r = 0.94, n = 15). However, NMDA- but not bradykinin (BK)-induced dilations of arteriolar sections over large veins were reduced by 31 +/- 1% (means +/- SE, P < 0.05, n = 4) compared with adjacent sections on the cortical surface. Also, 100 microM NMDA increased cerebrospinal fluid levels of NO metabolites from 3.7 +/- 1.0 to 5.3 +/- 1.2 microM (P < 0.05, n = 6). Endothelial stunning by intracarotid injection of phorbol 12,13-dibutyrate did not affect NMDA-induced vasodilation but attenuated vascular responses to hypercapnia and BK by approximately 70% (n = 7). Finally, miconazole (n = 6, 20 microM) pretreatment and coapplication with NMDA did not alter vascular responses to NMDA. In conclusion, NMDA appears to dilate pial arterioles exclusively through release and diffusion of NO from neurons to the pial surface in piglets.
Domoki
Ferenc
F
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157-1010, USA. domoki@phys.szote.u-szeged.hu
Perciaccante
James V
JV
Shimizu
Katsuyoshi
K
Puskar
Michelle
M
Busija
David W
DW
Bari
Ferenc
F
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004388:Dura Mater / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005260:Female; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D008853:Microscopy; D016202:N-Methylaspartate / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology*; D010841:Pia Mater / Q000098:blood supply*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016202:N-Methylaspartate; D008825:Miconazole