Role of Prostaglandins in the Response of the Cerebral Circulation to Carbon Dioxide in Conscious Rabbits

Abstract

The role of prostaglandins in maintenance of resting cerebral blood flow (CBF) and in cerebral vasodilatation during hypercapnia remains controversial. The effect of indomethacin, a cyclo-oxygenase inhibitor, on CBF and cerebrovascular resistance (CVR) was examined in conscious animals. Regional and total CBF were measured with radioactive microspheres, and the efficacy of blockade of prostaglandin synthesis by indomethacin was examined by the cranial window method. CBF was measured in conscious rabbits with 15-μm radioactive microspheres during normocapnia (Pco2 ≈ 30 mm Hg) and hypercapnia (Pco2 ≈ 60 mm Hg), before and after intravenous administration of indomethacin (10 mg/kg) or vehicle (n = 6 for each). Thus, each animal served as its own control. CBF was 84 ± 6 and 190 ± 27 (mean ± SE) ml/min/100 g during normocapnia and hypercapnia, respectively, before indomethacin, and 78 ± 5 ml/min/100 g during normocapnia and 180 ± 16 ml/min/100 g during hypercapnia following indomethacin. Thus, indomethacin did not change normocapnic CBF. In addition, cerebrovascular responses during hypercapnia did not vary between the indomethacin and vehicle groups. Indomethacin did not attenuate increases in blood flow in any area of the brain, except slightly to cerebellum during hypercapnia. Indomethacin did not affect CVR during normocapnia or hypercapnia. The topical application of arachidonic acid (75 and 150 μg/mg), dissolved in cerebrospinal fluid, dilated pial arteries in a dose-dependent fashion. Intravenous administration of indomethacin (10 mg/kg) blocked vasodilatation produced by arachidonic acid by 87% (p < 0.05). Thus, indomethacin, at a dose that effectively inhibits prostaglandin synthesis, did not change resting CBF or CVR or attenuate the increase in CBF or decrease in CVR during hypercapnia. These findings suggest that prostaglandins do not contribute significantly to regulation of the cerebral circulation during normocapnia and hypercapnia.