Indomethacin-sensitive CO2 reactivity of cerebral arterioles is restored by vasodilator prostaglandin.

To investigate the role of vasodilator prostanoids in the CO2-induced relaxation of cerebral arterioles, the present study examined the effect of exogenous prostaglandin (PG) E2 and nonprostanoid vasodilators, adenosine and sodium nitroprusside, on the indomethacin-impaired pial arteriolar response to CO2 in newborn piglets. Reactivity of pial arterioles (52-131 microns diam) was determined using a closed cranial window with intravital microscopy. Cortical prostanoid synthesis was assessed by analyzing for select prostanoids in cerebrospinal fluid sampled from under the cranial window. Inhalation of 7% CO2 caused an elevation of cortical 6-keto-PGF1 alpha and thromboxane (Tx) B2 and increased pial arteriolar diameter by 34 +/- 5%. Two cyclooxygenase inhibitors, indomethacin (5 mg/kg i.v.) and ibuprofen (30 mg/kg i.v.), abolished the CO2-induced elevation of cortical prostanoids. Indomethacin, but not ibuprofen, blocked the CO2-induced increase in pial arteriolar diameter. The indomethacin-impaired vasodilator response to CO2 was restored when PGE2 (0.1-1 microM) was applied topically to the cortical surface. Adenosine (1-100 microM) and sodium nitroprusside (0.5 microM) only partially restored the vasodilator response to CO2. The data suggest that vasodilator prostanoids facilitate cerebrovascular relaxation to CO2 and may play a permissive role in the relaxation response of vascular smooth muscle. The fact that adenosine (adenosine 3',5'-cyclic monophosphate-mediated dilator) and sodium nitroprusside (guanosine 3',5'-cyclic monophosphate-mediated dilator), were partially effective suggests a role for those intracellular signaling pathways. We speculate that receptor activation of intracellular pathways may alter Ca2+ sensitivity of the contractile apparatus in such a way that the relaxation response to CO2 can occur.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dexamethasone on cerebral prostanoid formation and pial arteriolar reactivity to CO2 in newborn pigs.

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.

Effect of indomethacin on the regulation of cerebral blood flow during respiratory alkalosis in newborn piglets.

The effect of cyclooxygenase inhibition by indomethacin on regional cerebral blood flow (CBF) during hypocapnia induced by hyperventilation and during hypercapnia induced by CO2 inhalation was examined. CBF was measured in 27 anesthetized, ventilated piglets (2-8 d) using microspheres in control and indomethacin treated animals (5 mg/kg) after hyperventilation or inhalation of 6% CO2. In the control group (n = 6), CBF decreased significantly (p less than 0.05) to all regions of the brain after hyperventilation with a 32% decrease in the cerebral cortex. In the indomethacin-treated group (n = 6), blood flow significantly decreased by 35 to 49% in all regions of the brain, except the cerebral white matter, during normocapnia with no further decrease in flow during subsequent hypocapnia. Although CBF increased significantly after indomethacin treatment during hypercapnia the response was markedly attenuated with blood flow to the cerebral gray matter, hippocampus and pons rising only 42, 25, and 42% in contrast to 108, 75, and 225% in the control group. Since indomethacin decreased resting CBF, unilateral sympathetic nerve stimulation at 15 Hz was used to test the specificity of indomethacin on hypocapnic vasoconstriction (n = 5). Unilateral sympathetic nerve stimulation caused a further statistically significant decrease in CBF on the stimulated side after hyperventilation with indomethacin (12%), which was comparable to that which occurred during normocapnia (16%). The data demonstrate that indomethacin attenuates the cerebrovascular sensitivity to both increases and decreases in CO2/H+ and implicate a possible role for vasoactive prostanoids in mediating the response of CBF to fluctuations in CO2 in newborn piglets.

Hepatic disease associated with intrauterine parvovirus B19 infection in a newborn premature infant.

A hydropic premature infant with intrauterine growth retardation died at 4 days of age and was found at necropsy to have advanced liver disease. Clinical and serologic findings in mother and infant were consistent with recent parvovirus B19 infection. Parvovirus can cause fetal liver disease in animals, and some instances of congenital hepatic dysfunction in man may be due to intrauterine parvovirus B19 infection.