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 F2 alpha (PGF2 alpha) 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), PGF2 alpha (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 PGF2 alpha and U46619 resulted in dose-dependent cerebral vasoconstriction, and the dose-response curve for each agonist 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 microns (p less than 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.
Wagerle
L C
LC
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Busija
D W
DW
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001160:Arterioles / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002536:Cerebral Arteries / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004357:Drug Synergism; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D013552:Swine; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost; D000109:Acetylcholine; D009638:Norepinephrine