ACTION OF HEPARIN AND RUTHENIUM RED ON RESPONSES OF REVERSIBLY-PERMEABILIZED RAT MESENTERIC-ARTERIES

Heparin and ruthenium red were introduced intracellularly into rat mesenteric resistance arteries via reversible-permeabilisation. Heparin and ruthenium red inhibited contractile responses to noradrenaline, but not caffeine in Ca2+-free conditions. Neither heparin nor ruthenium red significantly inhibited peak contractile responses to K+, noradrenaline or caffeine in physiological saline, although heparin significantly increased the time taken for peak force to develop in response to noradrenaline. Noradrenaline and calcium concentration-response relationships were unaffected by heparin. Experiments with permeabilised, fura-2 loaded vessels indicated that heparin inhibited Ca2+ release induced by noradrenaline, but did not inhibit caffeine-induced Ca2+ release. The peak rise in intracellular Ca2+ following K+, or noradrenaline in physiological saline was unaffected by heparin. The use of reversible permeabilisation may prove a useful approach, allowing introduction of a variety of membrane-impermeant blockers of second messenger systems into intact resistance arteries.