Prostanoids in cortical subarachnoid cerebrospinal fluid and pial arterial diameter in newborn pigs.

Abstract

SUMMARY. These studies were designed to investigate the relationship between ceTebral prostanoid synthesis and pial arterial caliber in chloralose-anesthetized newborn pigs with normal blood gases and pH and during combined arterial hypoxia and hypercapnia. Piglets less than 5 days old were equipped with closed cranial windows to allow direct observation of pial vessels, application of prostaglandin E^ and sampling of cortical subarachnoid cerebrospinal fluid. We found that prostanoids accumulate in cerebrospinal fluid on the cortical surface. The only prostanoid detected in arterial blood was 6-keto-prostaglandin Fi o [442 ± 74 pg/ml (radioimmunoassay)]. Only small quantities of 6-keto-prostaglandin F la (214 ± 53 pg/ml) and thromboxane B? (122 ± 18 pg/ml) were found in cerebrospinal fluid from the cisterna magna. Higher concentrations of 6-keto-prostaglandin Fi o (1056 ± 159 pg/ml), thromboxane B 2 (229 ± 64 pg/ml), and prostaglandin E 2 (4235 ± 269 pg/ml) were found in cortical subarachnoid fluid. In contrast to arterial and asternal concentrations, the concentrations of 6-keto-prostaglandin F ]<u thromboxane Bz, and prostaglandin E 2 in cortical subarachnoid fluid wwe increased reversibly by ventilation with 9% carbon dioxide, 10% oxygen, (6-keto-prostaglandin F ]o/ 5436 ± 1576 pg/ml; thromboxane B2, 694 ± 122 pg/ml; and, prostaglandin E^ 12,455 ± 3688 pg/ml). Further, pial arteries dilated in response to topical application of prostaglandin E 2 at the concentration that was found in cortical subarachnoid fluid during combined hypoxia and hypercapnia. Systemic administration of indomethadn trihydrate (5 mg/kg) markedly reduced cortical subarachnoid fluid prostanoid concentrations and attenuated the pial artery vasodilation induced by combined hypoxia and hypercapnia. Our data are consistent with the hypothesis that cerebral prostanoids represent an integral component in cerebral hemodynamic control in the neonatal pig. (Circ Res 57: 689-694, 1985)

The Role of Endothelium and Nitric Oxide in Rat Pial Arteriolar Dilatory Responses to CO2 in vivo

“…Whether perivascular astrocytes, which may also contain constitutive NOS (Springall et aI., 1992;Murphy et aI., 1993), make any contribution to the hypercapnic response remains to be ad dressed in future investigations. Interestingly, in contrast to the results obtained in adult rats, cats, and dogs, vascular endothelium appears to represent an integral component of the cerebral vasodilatory response to hypercapnia in newborn pigs (Leffler and Busija, 1985;Leffler et aI., 1994). Hypercapnia stimulates cerebral micro vascular endothelial cells to produce vasodilatory prostanoids (Hsu et aI., 1994).…”

Hydrogen sulfide and cerebral microvascular tone in newborn pigs

“…Figure 10 is a simplified schematic diagram of two systems that appear to be involved in pial arteriolar dilation to hypercapnia in newborn pigs, CSE/H 2 S (present results) and prostaglandin cyclooxygenase/prostanoids (28,29,30). Regarding the role of endothelium and prostacyclin in cerebrovascular dilation to hypercapnia in the newborn, what initially appeared simple and straightforward turned out to be more complicated.…”

“…The permissive role may be contributory, secondary, or backup when prostanoids are allowed to increase rather than being held constant. Hypercapnia elevates dilator prostanoids in the newborn pig cortical CSF sufficiently that higher levels at sites of production could explain the pial arteriolar dilation to hypercapnia via elevation of cAMP (29,30). Whether or not the elevation of prostacyclin and PGE 2 plays a direct role in causing hypercapnia-induced dilation when prostanoid production is not inhibited is not known.…”

Vascular responses to vasopressin are tone-dependent in the cerebral circulation of the newborn pig.

“…15 Antibodies to 6-keto-PGF )a , thromboxane (TX)B 2 , PGEj, and PGF^ were produced in rabbits immunized with prostanoids coupled to thyroglobulin using the mixed anhydride method. Cross reactivities of the prostanoid antibodies with other prostanoids studied were all below 1%.…”