KETAMINE RELAXES RABBIT FEMORAL ARTERIES BY REDUCING [CA-2-C ACTIVITY(]I AND PHOSPHOLIPASE)

The effects of the short-acting anesthetic, ketamine, on intracellular free Ca2+ concentrations, ([Ca2+]i), inositol phosphate levels and fo rce produced by contractile agonists were investigated in strips of ra bbit femoral artery. In concentration-response curves, ketamine produc ed an insurmountable inhibition of contractions produced by KCl and th e L-type Ca2+ channel agonist, Bay k 8644. However, in K+-depolarized tissues, high concentrations of CaCl2 could overcome the inhibition pr oduced by ketamine, suggesting that ketamine may have competed with Ca 2+ in activated L-type Ca2+ channels. In support of the contention tha t it inhibits L-type Ca2+ channels, ketamine was found to concomitantl y reduce the levels of force and [Ca2+]i produced by 50 mM KCl. Ketami ne reduced the potency, but not the maximum force, produced by phenyle phrine. However, this surmountable inhibition may have been due to act ivation of 'spare' alpha-adrenoceptors rather than to competition of r eceptor binding because, after phenoxybenzamine pretreatment to reduce alpha-adrenoceptor numbers, phenylephrine concentration-response curv es in the presence of ketamine were insurmountable. Ketamine at 0.32 m M reduced the transient contractions produced in a Ca2+-free solution and the increase in phospholipase C activity (estimated by measuring i nositol phosphate production in the presence of Li+) produced by 1 but not 10 uM phenylephrine. These data suggest that ketamine inhibited c ontractions produced in rabbit femoral artery by decreasing Ca2+ chann el activity and by reducing phospholipase C activation.