Light/dye microvascular injury selectively eliminates hypercapnia-induced pial arteriolar dilation in newborn pigs.
Cerebral vasodilation in response to hypercapnia involves prostanoids in newborn pigs. This study examines the hypothesis that endothelial injury in vivo inhibits cerebral vasodilation and prostacyclin synthesis in response to hypercapnia, thus suggesting prostacyclin is a primary endothelium-derived vasodilating factor in newborn pig cerebral circulation. Anesthetized piglets with closed cranial windows were studied before and after injury caused by light/dye or before and after dye-only sham control. Light/dye injury was produced by injecting sodium fluorescein intravenously and passing filtered light from a mercury arc lamp through the cranial window. Ultrastructural changes to endothelium of pial vessels were produced that were characterized by surface pits, vacuolar cytoplasmic inclusions, and mitochondrial injury. After the light/dye injury, dilation to hypercapnia was absent while dilations to iloprost, isoproterenol, and sodium nitroprusside and constrictions to norepinephrine and acetylcholine were retained. Before light/dye treatment, hypercapnia increased cortical periarachnoid 6-keto prostaglandin F1 alpha concentration approximately threefold. However, after treatment, 6-keto-prostaglandin F1 alpha was not increased significantly in response to hypercapnia. These findings are consistent with the hypothesis that endothelial prostacyclin synthesis induced by hypercapnia participates in dilation of adjacent smooth muscle.
Leffler
C W
CW
Department of Physiology, University of Tennessee, Memphis 38163.
Mirro
R
R
Shanklin
D R
DR
Armstead
W M
WM
Shibata
M
M
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D002245:Carbon Dioxide / Q000097:blood; D019793:Fluorescein; D005452:Fluoresceins / Q000633:toxicity*; D006935:Hypercapnia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D016285:Iloprost / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008027:Light / Q000009:adverse effects*; D009131:Muscle, Smooth, Vascular / Q000473:pathology* / Q000503:physiopathology / Q000648:ultrastructure; D009599:Nitroprusside / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D010296:Parietal Lobe / Q000187:drug effects / Q000648:ultrastructure; D010313:Partial Pressure; D010841:Pia Mater / Q000098:blood supply*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects
D005452:Fluoresceins; D002245:Carbon Dioxide; D009599:Nitroprusside; D016285:Iloprost; D007545:Isoproterenol; D010100:Oxygen; D019793:Fluorescein