Ketamine relaxes rabbit femoral arteries by reducing [Ca 2+] i and phospholipase C activity

Abstract

The effects of the short-acting anesthetic, ketamine, on intracellular free Ca 2+ concentrations, ([Ca 2+] 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 Ca 2+ channel agonist, Bay k 8644. However, in K + -depolarized tissues, high concentrations of CaCl 2 could overcome the inhibition produced by ketamine, suggesting that ketamine may have competed with Ca 2+ in activated L-type Ca 2+ channels. In support of the contention that it inhibits L-type Ca 2+ channels, ketamine was found to concomitantly reduce the levels of force and [Ca 2+] 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’ α-adrenoceptors rather than to competition of receptor binding because, after phenoxybenzamine pretreatment to reduce α-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 μM phenylephrine. These data suggest that ketamine inhibited contractions produced in rabbit femoral artery by decreasing Ca 2+ channel activity and by reducing phospholipase C activation.