Prostacyclin receptor activation and pial arteriolar dilation after endothelial injury in piglets.
OBJECTIVE
Both light/dye endothelial injury and indomethacin treatment inhibit hypercapnia-induced cerebral prostacyclin synthesis and pial arteriolar dilation in newborn pigs. Topical iloprost can allow hypercapnia-induced dilation of pial arterioles to occur in piglets treated with indomethacin. We addressed the hypothesis that prostacyclin receptor activation with iloprost can return the ability of pial arterioles with endothelial injury to respond to hypercapnia. We also examined whether the endothelial dependence and the permissive role of prostacyclin extended to histamine-induced dilation or are specific for hypercapnia.


METHODS
Experiments used chloralose-anesthetized piglets equipped with closed cranial windows. Hypercapnia (PaCO2 approximately 80 mm Hg) and topically applied histamine (10(-6) and 10(-5) mol/L) dilated pial arterioles. Dilations in response to both stimuli were abolished by light/dye treatment.


RESULTS
Simultaneous topical treatment with iloprost (10(-12) mol/L, which caused no residual dilation, returned dilation of pial arterioles to both hypercapnia and histamine. On removal of iloprost, responses were again absent and returned with readdition of iloprost to the cortical cerebrospinal fluid. Neither isoproterenol nor sodium nitroprusside returned responses to hypercapnia after light/dye treatment.


CONCLUSIONS
These data add further support to the hypothesis that prostacyclin represents an important endothelial-derived signal in the newborn pig cerebral circulation that can permit appropriate responses by adjacent smooth muscle in response to specific stimuli.
D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D002536:Cerebral Arteries / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D004396:Coloring Agents; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006935:Hypercapnia / Q000188:drug therapy; D016285:Iloprost / Q000494:pharmacology*; D008027:Light; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D004396:Coloring Agents; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D014665:Vasodilator Agents; D006632:Histamine; D016285:Iloprost