Bradykinin modulates arginine vasopressin-induced calcium influx in vascular myocytes.
We investigated direct, endothelium-independent effects of bradykinin on arginine vasopressin-induced calcium influx in vascular smooth muscle cells. We studied cultured rat vascular smooth muscle cells by using the whole-cell 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 increase in [Ca2+]i. This was readily reversible (n=28). At a holding potential of -40 to -60 mV, arginine vasopressin induced a sustained inward current correlated with a sustained increase in [Ca2+]i. Bradykinin (30 nM to 30 microM) had no effect on arginine vasopressin-induced [Ca2+]i transients. However, during the sustained phase of increased [Ca2+]i, bradykinin reversibly attenuated relative fluorescence and inward current in the presence of arginine vasopressin (n=14). This was concentration dependent and inhibited by [D-Phe7]-bradykinin (30 microM), a kinin receptor antagonist. Also, sustained arginine vasopressin-mediated increases in [Ca2+]i and inward current were attenuated by Ca2+-free or La3+-supplemented perfusate but not 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 bradykinin 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-insensitive, Ca2+-conducting inward current.
Pieper
S J
SJ
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Fenton
A M
AM
Kurachi
Y
Y
Shen
W K
WK
D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D018929:Cell Culture Techniques; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D001127:Arginine Vasopressin; D001920:Bradykinin; D002118:Calcium