Ca2+ entry blockers inhibit prostaglandin F2 alpha-induced cerebrovascular contractile responses in goats.
We examined the effects of extracellular Ca2+ withdrawal and of Ca2+ entry blockers on goat cerebrovascular responses to prostaglandin F2 alpha (PGF2 alpha). We measured isometric tension in isolated middle cerebral arteries, and cerebral blood flow (CBF) in unanesthetized animals. PGF2 alpha produced concentration-dependent contractions of isolated arteries. The contractions were partially inhibited by incubation in Ca(2+)-free medium (by 63.1 +/- 1.8% without ethyleneglycol-bis-(beta-amino-ethylether)-N,N,N',N'-tetra-a cetate (EGTA), and by 82.4 +/- 3.7% with EGTA). The Ca2+ entry blockers inhibited PGF2 alpha-elicited contraction and relaxed PGF2 alpha-precontracted arteries (nicardipine, 91.4 +/- 9.8%; nimodipine, 73.1 +/- 2.0%; and verapamil, 50.5 +/- 4.5% relaxation of the active tone). Injection of PGF2 alpha into the cerebral circulation produced dose-dependent reductions in CBF (34.4 +/- 2.1% after 30 micrograms) which were inhibited during infusion of Ca2+ entry blockers (nicardipine 10 micrograms/min, 14.7 +/- 1.5%; nimodipine 10 micrograms/min, 13.6 +/- 1.3%; and verapamil 100 micrograms/min, 13.7 +/- 2.3% of flow reduction). We conclude that PGF2 alpha-elicited contraction of goat cerebral arteries is mainly mediated by extracellular Ca2+ influx through Ca2+ channels sensitive to Ca2+ entry blockers. The anticonstrictor effects of Ca2+ entry blockers observed in vitro are consistent with their inhibitory effect on the PGF2 alpha-induced CBF reductions.
Salom
J B
JB
Centro de Investigación, Hospital La Fe, Valencia, Valencia, Spain.
Torregrosa
G
G
Miranda
F J
FJ
Alabadí
J A
JA
Alvarez
C
C
Alborch
E
E
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D006041:Goats; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004533:Egtazic Acid; D015237:Dinoprost; D002118:Calcium