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.