N-methyl-D-aspartate-induced vasodilation is mediated by endothelium-independent nitric oxide release in piglets
Autor: | Michelle Puskar, James V. Perciaccante, Katsuyoshi Shimizu, Ferenc Domoki, David W. Busija, Ferenc Bari |
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Rok vydání: | 2002 |
Předmět: |
Epoxygenase
Male N-Methylaspartate Endothelium Miconazole Physiology Swine Bradykinin Vasodilation Pharmacology Nitric Oxide Receptors N-Methyl-D-Aspartate Nitric oxide chemistry.chemical_compound Arteriole Physiology (medical) medicine.artery medicine Animals Microscopy biology Chemistry Endothelial stem cell Arterioles medicine.anatomical_structure nervous system Animals Newborn Anesthesia biology.protein NMDA receptor Pia Mater Female Dura Mater Endothelium Vascular Cardiology and Cardiovascular Medicine |
Zdroj: | American journal of physiology. Heart and circulatory physiology. 282(4) |
ISSN: | 0363-6135 |
Popis: | 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, P0.05, 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 (P0.05, 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. |
Databáze: | OpenAIRE |
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