Mechanism of CO2 response in cerebral arteries of the newborn pig: role of phospholipase, cyclooxygenase, and lipoxygenase pathways.
The role of phospholipase, lipoxygenase, and cyclooxygenase pathways in the mechanism of the cerebrovascular response to CO2 and H+ was investigated in newborn piglets. Responsiveness of pial arterioles, 48-206 micron diameter, to inhalation of 6% CO2 and to suffusion of acidic cerebrospinal fluid (CSF, pH = 6.84), adenosine (10(-4) M), or theophylline (10(-2) M) was studied using a closed cranial window. Pial arteriolar diameter was measured using intravital microscopy. Phospholipase inhibitors quinacrine hydrochloride (10(-4) M in CSF) and p-bromophenacyl bromide (10(-4) M in CSF) abolished the CO2 vasodilation from delta diameter = 27 +/- 5% and 28 +/- 3% during baseline to 0 +/- 4% and -1 +/- 1% following the respective inhibitors. Following administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg i.v.), the CO2 response was converted from vasodilation, 31 +/- 6%, to constriction, -4 +/- 1% (p less than 0.001), while the lipoxygenase inhibitor nordihydroguaiaretic acid (2 mg/kg i.v. or 10(-4) M in CSF) augmented the pial arteriolar response to CO2 from 21 +/- 4% to 34 +/- 7% (p less than 0.005). Topical application of superoxide dismutase (40 units/ml CSF) plus catalase (40 units/ml CSF) also appeared to augment the CO2 response. Suffusion of the cortical surface with acidic CSF at constant PCO2 increased pial arteriolar diameter by 11 +/- 2% that was also abolished by indomethacin. Vasodilatory responses to topical adenosine and theophylline were not affected by indomethacin, suggesting specificity for H+ ion-related vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects; D002245:Carbon Dioxide / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008084:Lipoxygenase / Q000502:physiology; D009637:Masoprocol / Q000494:pharmacology; D010741:Phospholipases A / Q000502:physiology; D010841:Pia Mater / Q000098:blood supply; D011451:Prostaglandin-Endoperoxide Synthases / Q000502:physiology; D011796:Quinacrine / Q000494:pharmacology; D013552:Swine
D000098:Acetophenones; D002245:Carbon Dioxide; D009637:Masoprocol; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D011796:Quinacrine; C006821:4-bromophenacyl bromide; D007213:Indomethacin