Digoxin-norepinephrine response and calcium blocker effects in vascular smooth muscle

The mechanism of potentiation by digoxin of the response of vascular smooth muscle to norepinephrine was investigated in 5-cm intact segments of rabbit carotid artery. Segments were mounted in a chamber and perfused at constant pressure while flow and upstream and downstream pressures were recorded and resistance was calculated. Each vessel was perfused with a submaximal vasoconstricting concentration of norepinephrine (6 x 10(-6)M) alone, in the presence of digoxin (6 x 10(-5)M), and during exposure to both digoxin and one of the following calcium antagonists: lanthanum chloride (5 x 10(-4)M procaine hydrochloride (5 x 10(-3)M), or verapamil (5 x 10(-5)M). Digoxin potentiated the response to norepinephrine alone by 20% (P less than 0.01), to norepinephrine plus lanthanum chloride by 10% (P less than 0.001), and to norepinephrine plus procaine hydrochloride by 17% (P less than 0.001). Digoxin did not potentiate the norepinephrine response in the presence of verapamil. These data suggest that the mechanism of digoxin potentiation of the norepinephrine response in vascular smooth muscle may involve an alteration in a cellular calcium sequestration or release process. The potential cellular sites that may contribute to this phenomenon are discussed.