title: Effect of dexamethasone on cerebral prostanoid formation and pial arteriolar reactivity to CO2 in newborn pigs.
abstract: This study investigates the effect of glucocorticoid treatment on the relationship between arteriolar PCO2 and cortical prostanoid production and on cerebrovascular responsiveness to elevated CO2 in newborn piglets. The response of pial arteries to hypercapnia (fractional inspired CO2 = 0.035 and 0.07) was studied in 18 anesthetized newborn piglets, 9 of which were pretreated with dexamethasone (2 mg.kg-1.day-1 for 36-48 h). Pial arterioles (77-122 microns diam) were monitored using a closed cranial window and intravital microscopy. Perivascular cerebrospinal fluid (CSF) was sampled from the cortical surface and analyzed for 6-keto-prostaglandin F1 alpha and thromboxane B2 (TxB2) using radioimmunoassay. In the dexamethasone-treated animals the increase in arteriolar diameter to CO2 was diminished by approximately 50% for each respective CO2 concentration vs. the control group. Acute sympathetic denervation did not restore the CO2 dilator response. Dexamethasone did not alter baseline cortical CSF prostanoid concentrations but abolished the CO2-induced increase in CSF prostanoids. The dilator response to exogenously applied prostaglandin E2 was inhibited in dexamethasone-treated animals. However, the dilator response to exogenous adenosine and the contractile response to prostaglandin F2 alpha were not altered in the dexamethasone-treated piglets. The data support the concept that metabolites of arachidonic acid participate in the cerebrovascular response to CO2 and suggest that glucocorticoid treatment may influence cerebrovascular tone via this mechanism.
authors.affiliation: Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: L C
authors.initials: LC
authors.lastname: Wagerle
authors.forename: P A
authors.initials: PA
authors.lastname: DeGiulio
authors.forename: O P
authors.initials: OP
authors.lastname: Mishra
authors.forename: M
authors.initials: M
authors.lastname: Delivoria-Papadopoulos
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001160:Arterioles / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002245:Carbon Dioxide / Q000097:blood / Q000494:pharmacology*; D003714:Denervation; D003907:Dexamethasone / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D011453:Prostaglandins / Q000096:biosynthesis*; D013552:Swine; D013564:Sympathetic Nervous System / Q000502:physiology; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D014664:Vasodilation / Q000187:drug effects
chemical_list: D011453:Prostaglandins; D002245:Carbon Dioxide; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003907:Dexamethasone; D015237:Dinoprost; D000241:Adenosine; D015232:Dinoprostone