Vascular responses of ophthalmic arteries to exogenous and endogenous norepinephrine

A participation of neuronal and tissue uptake mechanism in responses to periarterial electrical sympathetic nerve stimulation (ES) and intra-arterial applications of norepinephrine (NE) was investigated in the isolated and perfused canine ophthalmic arteries (OA), using key pharmacological drugs such as imipramine, tyramine, cocaine, cortisol and diltiazem. Results were as follows: (1) NE, KCl and ES induced marked vasoconstrictions in a dose- and frequency-related manner, but tyramine induced only a slight constriction even at large doses; (2) cortisol, an uptake2 blocker, did not significantly modify KCl- and ES-induced vasoconstrictions, but significantly enhanced NE-induced responses; (3) small doses of imipramine, a neuronal uptake1 blocker, did not modify NE-induced vasoconstrictions, but large doses decreased them. On the other hand, the ES-induced response was slightly increased by a relative small dose of imipramine; (4) cocaine, another uptake1 blocker, slightly enhanced NE- and ES-induced responses; (5) ES-induced response was reduced by not only diltiazem, but also Ca2+-free solution with EGTA (1 mM l-1). The NE-induced response was not affected by diltiazem (Ohkubo and Chiba, 1987, Exp. Eye Res. 45, 263-70), and slightly but significantly depressed by Ca2+-free solution with EGTA. These results suggest that tissue and neuronal uptake mechanisms exist in responses to ES and NE1, the response to ES was markedly dependent on Ca2+ influx to the cell membrane2, and exogenous NE may induce Ca2+ movement mainly from the intracellular store site.