Cholinergic mechanisms in the cerebral circulation of the newborn piglet: Effect of inhibitiors of arachidonic acid metabolism

Abstract

The cerebrovascular response to cholinergic stimulation and the effect of inhibition of the lipoxygenase and cyclooxygenase pathways on the response to acetylcholine (ACh) was investigated in newborn piglets. Responsiveness of pial arterioles to ACh, methacholine, and nicotine was studied using a closed cranial window. Pial arteriolar diameter was measured using intravital microscopy. Pial arteriolar responses to ACh, 10-8-10-4 M, applied to the cortical surface, were variable and dose-dependent. At low concentration, 10-7 M, 45% of the arterioles increased diameter by 9 ± 1%, 19% responded by decreasing diameter by 9 ± 1%, and 35% did not respond. The response to high concentration, 10-4 M, was a profound decrease in diameter, 28 ± 3%, in 78% of the arterioles studied. These effects were abolished by atropine (0.5 mg/kg i.v.). Muscarinic agonist, methacholine, 10-5-10-3 M, also resulted in a decreased in cerebral vascular diameter, while nicotine, 10-6-10-4 M, had no effect. In six animals, administration of cyclooxygenase inhibitor, indomethacin (5 mg/kg i.v.), blocked the response to 10-4 M ACh but did not affect the response to 10-7 M ACh. In five animals, administration of lipoxygenase inhibitor, norhydroguaiaretic acid (2 mg/kg i.v.) augmented the vasoconstrictor response at both ACh concentrations. The data suggest that, in the newborn piglet, vasoactive prostanoids released following cholinergic activation of a muscarinic-type receptor mediate vasoconstriction in cerebral arterioles.