PERMISSIVE ROLE OF PROSTACYCLIN IN CEREBRAL VASODILATION TO HYPERCAPNIA IN NEWBORN PIGS

Hypercapnic cerebral vasodilation in piglets is accompanied by increas ed cerebral prostanoid synthesis. Interventions that prevent the incre ased prostanoids also interfere with the vasodilation. However, the in creased prostanoids may not produce vasodilation directly; instead, th ey may allow or enhance function of another mechanism. The present exp eriments examined the hypothesis that prostacyclin can allow, but may not directly produce, cerebral vasodilation to hypercapnia. Chloralose -anesthetized piglets were equipped with closed cranial windows for me asurements of pial arteriolar diameters. Hypercapnia (arterial CO2 par tial pressure similar to 70 mmHg) was administered before and after in domethacin (5 mg/kg iv) in all animals. Then artificial cerebrospinal fluid (aCSF) under the cranial window was replaced for the remainder o f the experiment with aCSF containing vehicle, carbaprostacyclin (60 p M), iloprost (1 pM), prostaglandin E(2) (PGE(2); 1.7 and 3.3 nM), isop roterenol (10 and 100 nM), or sodium nitroprusside (1 mu M), and hyper capnia was repeated. The two prostacyclin receptor agonists restored c erebral vasodilation to hypercapnia that had been blocked by indometha cin (to 99 +/- 31% and 76 +/- 11% of the before-indomethacin dilation for carbaprostacyclin and iloprost, respectively.) The highest dose of PGE(2) partially restored the dilation (43 +/- 7% of the preindometha cin response). In contrast, neither isoproterenol nor sodium nitroprus side permitted significant dilation to hypercapnia following indometha cin treatment. These data indicate that prostacyclin can allow hyperca pnic vasodilation to occur, but increasing levels do not appear to be necessary to cause the dilation directly. The short half-life of prost acyclin may explain why active prostanoid synthesis appears to be nece ssary for hypercapnia-induced cerebral vasodilation in newborn pigs.