Ketamine relaxes rabbit femoral arteries by reducing [Ca2+]i and phospholipase C activity.
The effects of the short-acting anesthetic, ketamine, on intracellular free Ca2+ concentrations, ([Ca2+]i), inositol phosphate levels and force produced by contractile agonists were investigated in strips of rabbit femoral artery. In concentration-response curves, ketamine produced an insurmountable inhibition of contractions produced by KCl and the L-type Ca2+ channel agonist, Bay k 8644. However, in K(+)-depolarized tissues, high concentrations of CaCl2 could overcome the inhibition produced by ketamine, suggesting that ketamine may have competed with Ca2+ in activated L-type Ca2+ channels. In support of the contention that it inhibits L-type Ca2+ channels, ketamine was found to concomitantly reduce the levels of force and [Ca2+]i produced by 50 mM KCl. Ketamine reduced the potency, but not the maximum force, produced by phenylephrine. However, this surmountable inhibition may have been due to activation of 'spare' alpha-adrenoceptors rather than to competition of receptor binding because, after phenoxybenzamine pretreatment to reduce alpha-adrenoceptor numbers, phenylephrine concentration-response curves in the presence of ketamine were insurmountable. Ketamine at 0.32 mM reduced the transient contractions produced in a Ca(2+)-free solution and the increase in phospholipase C activity (estimated by measuring inositol phosphate production in the presence of Li+) produced by 1 but not 10 microM phenylephrine. These data suggest that ketamine inhibited contractions produced in rabbit femoral artery by decreasing Ca2+ channel activity and by reducing phospholipase C activation.
Ratz
P H
PH
Department of Pharmacology, Eastern Virginia Medical School, Norfolk 23501.
Callahan
P E
PE
Lattanzio
F A
FA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005263:Femoral Artery / Q000187:drug effects; D066298:In Vitro Techniques; D007649:Ketamine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D011817:Rabbits; D010738:Type C Phospholipases / Q000378:metabolism*
D010716:Phosphatidylinositols; D010656:Phenylephrine; D007649:Ketamine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D010738:Type C Phospholipases; D002118:Calcium