Bradykinin modulates arginine vasopressin-induced calcium influx in vascular myocytes

We investigated direct, endothelium-independent effects of bradykinin on ar ginine vasopressin-induced calcium influx in vascular smooth muscle cells. We studied cultured rat vascular smooth muscle cells by using the whole-cel l voltage-clamp and calcium fluorescence imaging methods. Exposing cultured vascular smooth muscle cells (A7r5 cell line) to arginine vasopressin (100 nM) produced a transient increase in [Ca2+](i), followed by a sustained in crease in [Ca2+](i). This was readily reversible (n=28). At a holding poten tial of -40 to -60 mV, arginine vasopressin induced a sustained inward curr ent correlated with a sustained increase in [Ca2+](i). Bradykinin (30 nM to 30 mu M) had no effect on arginine vasopressin-induced [Ca2+](i) transient s. However, during the sustained phase of increased [Ca2+](i), bradykinin r eversibly attenuated relative fluorescence and inward current in the presen ce of arginine vasopressin (n=14), This was concentration dependent and inh ibited by [D-Phe(7)]-bradykinin (30 mu M), a kinin receptor antagonist. Als o, sustained arginine vasopressin-mediated increases in [Ca2+](i) and inwar d current were attenuated by Ca2+-free or La3+-supplemented perfusate but n ot by nifedipine (n=5). Conclusions: (1) Bradykinin can attenuate arginine vasopressin-induced and sustained Ca2+ influx and sustained inward current through a novel endothelium-independent process. (2) The direct effect of b radykinin on arginine vasopressin-induced increases in [Ca2+](i) sustained Ca2+ influx in vascular smooth muscle cells is concentration dependent and kinin-receptor mediated. (3) Arginine vasopressin-induced sustained [Ca2+]( i) elevation correlates with the activation of a dihydropyridine-insensitiv e, Ca2+-conducting inward current. (C) 1999 Elsevier Science Ireland Ltd. A ll rights reserved.