EFFECT OF THROMBOXANE-A2 ENDOPEROXIDE ANTAGONIST SQ29548 ON THE CONTRACTILE RESPONSE TO ACETYLCHOLINE IN NEWBORN PIGLET CEREBRAL-ARTERIES

Previous studies have shown that cholinergic stimulation results in a prostanoid-dependent cerebral vasoconstriction in piglets. The present study specifically investigated the contribution of thromboxane A2 (TXA2)/prostaglandin endoperoxide and prostaglandin F(2α) (PGF(2α)) to the cerebral vascular response to exogenous acetylcholine (ACh). Effects of TXA2/prostaglandin endoperoxide-receptor antagonist SQ29548 on responsiveness of pial arterioles to ACh (10-7 and 10-4 M), PGF(2α) (10-7-10-5 M), TXA2 mimetic 9,11-methanoepoxy prostaglandin H2 (U46619, 5 and 10 ng/ml), and norepinephrine (10-6-10-4 M) were studied by use of a closed cranial window in 37 anesthetized mechanically ventilated newborn piglets. Pial arteriolar diameter was measured by intravital microscopy. Topical application of exogenous PGF(2α) and U46619 resulted in dose-dependent cerebral vasoconstriction, and the dose-response curve for each agnonist was shifted to the right by the increasing concentrations of SQ29548 (10-6-10-8 M). Topical application of high concentration of ACh (10-4 M) caused a transient 34±4% decrease in pial arteriolar diameter from 98±6 to 65±5 μm (p<0.05). This constriction was attenuated (16±3%) in the presence of 10-8 M SQ29548 and abolished with 10-6 or 10-4 M SQ29548. SQ29548 (10-6 M) was without effect on the vasoconstrictor response to exogenous norepinephrine. Low concentration of ACh (10-7 M) had no consistent effect on pial arterioles in the absence or presence of TXA2/prostaglandin endoperoxide-receptor blockade. The data suggest that vascular prostaglandin/endoperoxide receptors mediate cerebral vasoconstriction upon muscarinic-receptor stimulation.