Multiple Actions of Phencyclidine and (+)MK-801 on Isolated Bovine Cerebral Arteries

• Published in: Journal of neurosurgical anesthesiology Vol. 30; no. 4; pp. 359 - 367
• Main Authors: Wendling, Woodrow W, Chen, Dong, Wendling, Karen S, Kamel, Ihab R
• Format: Journal Article
• Language: English
• Published: United States 01-10-2018
• Subjects: Animals; Calcium - metabolism; Calcium Channel Blockers - pharmacology; Cattle; Dizocilpine Maleate - pharmacology; Dose-Response Relationship, Drug; Excitatory Amino Acid Antagonists - pharmacology; In Vitro Techniques; Isometric Contraction - drug effects; Middle Cerebral Artery - drug effects; Middle Cerebral Artery - metabolism; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Phencyclidine - antagonists & inhibitors; Phencyclidine - pharmacology; Potassium Channel Blockers - pharmacology; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Thromboxane A2 - pharmacology
• ISSN: 0898-4921; 1537-1921
• DOI: 10.1097/ANA.0000000000000463

This study examines the direct effects of 3 noncompetitive N-methyl-D-aspartate receptor antagonists, phencyclidine (PCP), (+)MK-801, and (-)MK-801, on bovine middle cerebral arteries (BMCA). Rings of BMCA were mounted in isolated tissue chambers equipped with isometric tension transducers to obtain pharmacologic dose-response curves. In the absence of endogenous vasoconstrictors, the 3 N-methyl-D-aspartate antagonists each produced direct constriction of BMCA. The thromboxane A2 receptor antagonist SQ-29,548, the TxA2 synthase inhibitor furegrelate, the calcium antagonist nimodipine, and calcium-deficient media all inhibited maximal phencyclidine or (+)MK-801-induced constriction. Direct constriction by PCP or (+)MK-801 was independent of the presence of endothelium. When BMCA were preconstricted with potassium-depolarizing solution, PCP, (+)MK-801, and (-)MK-801 each produced only concentration-dependent relaxation. When BMCA were preconstricted with the stable TxA2 analog U-46,619 and exposed to increasing concentrations of PCP, (+)MK-801, or (-)MK-801, tension increased. Thromboxane A2 may contract BMCA by acting as a potassium channel blocker; iberiotoxin and tetraethylammonium both constrict BMCA. In Ca-deficient media containing either potassium or U-46,619, phencyclidine and (+)MK-801 each produced competitive inhibition of subsequent Ca-induced constriction. In additional experiments, arterial strips were mounted in isolated tissue chambers to directly measure calcium uptake, using Calcium as a radioactive tracer. Both phencyclidine and (+)MK-801 blocked potassium-stimulated or U-46,619-stimulated Ca uptake into arterial strips. These results suggest that phencyclidine and (+)MK-801 have 2 separate actions on BMCA. They may constrict arterial rings by releasing TxA2 from cerebrovascular smooth muscle, and relax arterial rings by acting as calcium antagonists.