Evidence of a direct constrictor action of MK-801 and its modulation by the endothelium in cerebral arteries.
The effects of MK-801 on the cerebral arteries and the possible involvement of the endothelium in such a response were examined using two experimental approaches: in vivo, by recording cerebral blood flow (CBF) in the unanesthetized goat, and in vitro, by recording isometric tension in goat and human cerebral arteries. Injection of increasing doses (3, 10, 30, and 100 micrograms) of MK-801 directly into the cerebroarterial supply elicited decreases in CBF and increases in cerebral vascular resistance (CVR; for the highest dose tested CBF decreased by 16 +/- 10% and CVR increased by 18 +/- 10%, p < 0.05). Administration of MK-801 as a single intravenous bolus (0.2 mg kg-1) reproduced that vasoconstrictor response (CBF decreased by 17 +/- 9% and CVR increased by 46 +/- 33%, p < 0.05), and it was followed by a phase of sustained tachycardia (26 +/- 15% increase in resting heart rate, p < 0.01) and hypertension (34 +/- 17% increase in resting mean arterial blood pressure, p < 0.05). In the in vitro experiments, addition of cumulative concentrations (10(-6) to 3 x 10(-4) M) of MK-801 elicited concentration-related contractions of goat and human cerebral arteries at both resting and active tone (10(-5) M prostaglandin F2 alpha).(ABSTRACT TRUNCATED AT 250 WORDS)
Centro de Investigación Hospital Universitario La Fe, Valencia, Spain.
G
G
Torregrosa
J B
JB
Salom
T
T
Jover
J A
JA
Alabadí
F J
FJ
Miranda
E
E
Alborch
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D006041:Goats; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction; D019335:Nitroarginine; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D016291:Dizocilpine Maleate; D001120:Arginine