Permissive role of prostacyclin in cerebral vasodilation to hypercapnia in newborn pigs

Charles Leffler, R. Mirro, L. J. Pharris, M. Shibata

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Hypercapnic cerebral vasodilation in piglets is accompanied by increased cerebral prostanoid synthesis. Interventions that prevent the increased prostanoids also interfere with the vasodilation. However, the increased prostanoids may not produce vasodilation directly, instead, they may allow or enhance function of another mechanism. The present experiments 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 measurements of pial arteriolar diameters. Hypercapnia (arterial CO2 partial pressure ~70 mmHg) was administered before and after indomethacin (5 mg/kg iv) in all animals. Then artificial cerebrospinal fluid (aCSF) under the cranial window was replaced for the remainder of the experiment with aCSF containing vehicle, carbaprostacyclin (60 pM), iloprost (1 pM), prostaglandin E2 (PGE2; 1.7 and 3.3 nM), isoproterenol (10 and 100 nM), or sodium nitroprusside (1 μM), and hypercapnia was repeated. The two prostacyclin receptor agonists restored cerebral vasodilation to hypercapnia that had been blocked by indomethacin (to 92 ± 31% and 76 ± 11% of the before-indomethacin dilation for carbaprostacyclin and iloprost, respectively.) The highest dose of PGE2 partially restored the dilation (43 ± 7% of the preindomethacin response). In contrast, neither isoproterenol nor sodium nitroprusside permitted significant dilation to hypercapnia following indomethacin treatment. These data indicate that prostacyclin can allow hypercapnic vasodilation to occur, but increasing levels do not appear to be necessary to cause the dilation directly. The short half-life of prostacyclin may explain why active prostanoid synthesis appears to be necessary for hypercapnia-induced cerebral vasodilation in newborn pigs.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume267
Issue number1 36-1
StatePublished - Jan 1 1994

Fingerprint

Hypercapnia
Epoprostenol
Vasodilation
Swine
Indomethacin
Prostaglandins
Dilatation
Dinoprostone
Iloprost
Nitroprusside
Isoproterenol
Cerebrospinal Fluid
Epoprostenol Receptors
Chloralose
Partial Pressure
Half-Life

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Permissive role of prostacyclin in cerebral vasodilation to hypercapnia in newborn pigs. / Leffler, Charles; Mirro, R.; Pharris, L. J.; Shibata, M.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 267, No. 1 36-1, 01.01.1994.

Research output: Contribution to journalArticle

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