CHOLINERGIC MECHANISM IN THE CEREBRAL CIRCULATION OF THE NEWBORN PIGLET

Abstract

We have shown that, in newborn piglets, the vasodilatory response to 0.1 μM acetylcholine (ACh) is modest (Δ diam = +9±1% in 45% of the vessels, mean±SE), the predominant response is vasoconstriction to 100 μM ACh (Δ diam = −28±3% in 78% of the vessels), and is associated with release of vasoactive prostanoids. The present study investigates the mechanism of the vasoconstrictor response to ACh in 15 anesthetized, mechanically ventilated piglets by examining a) the cholinergic receptor subtype involved, and b) the potential role of prostanoid release. Using a closed cranial window, ACh (0.1 and 100 μM in CSF) was applied to the pial surface and arteriolar diameter measured with video dimension analysis system. Thirty vessels ranging in diameter from 44 to 204 μm were studied. In five piglets, pretreated with muscarinic antagonist atropine (0.5 mg/kg, I.V.), ACh had no effect on arteriolar diameter (Δ diam=+3±2 and 0±4% at respective concentrations, n=15). In 4 piglets, the muscarinic agonist, methacholine (100 μM), caused vasoconstriction (Δdiam = −15±6%, n=4) while nicotine had no effect. In 6 animals, administration of cycooxygenase inhibitor sodium indomethachin trihydrate (5 mg/kg, I.V.) also prevented the vasoconstrictor effect of 100 μM ACh (Δ diam = −3±2%, n=11). Indomethacin did not reveal a vasodilatory response to 0.1 μM ACh (Δ diam=+3±1%). The data suggest that, in the newborn piglet, the cerebral vasoconstrictor response to the parasympathetic neurotransmitter ACh results from muscarinic receptor activation and may be mediated by vasoactive product of the cyclooxygenase pathway. (NIH #RO1-20337 and #R23-19762-01)