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Ca 2+ influx in the endothelial cells is required for the bradykinin‐induced endothelium‐dependent contraction in the porcine interlobar renal artery
Author(s) -
Ihara Eikichi,
Derkach Dmitry N.,
Hirano Katsuya,
Nishimura Junji,
Nawata Hajime,
Kanaide Hideo
Publication year - 2001
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2001.t01-1-00701.x
Subject(s) - bradykinin , contraction (grammar) , extracellular , chemistry , medicine , endocrinology , endothelium , biophysics , biology , biochemistry , receptor
1 To determine the mechanism of bradykinin‐induced production of endothelium‐derived contracting factors, we monitored the changes in cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in in situ endothelial cells in porcine aortic valvular strips and the changes in [Ca 2+ ] i of smooth muscle cells and force in porcine interlobar renal arterial strips using front‐surface fluorometry of fura‐2. 2 In the presence of N ω ‐nitro‐ l ‐arginine methyl ester, bradykinin caused an endothelium‐dependent transient elevation of [Ca 2+ ] i and contraction in smooth muscle in the interlobar renal artery. This contraction was completely inhibited by a prostaglandin H 2 /thromboxane A 2 receptor antagonist. 3 In the absence of extracellular Ca 2+ , bradykinin failed to induce contraction. However, replenishing extracellular Ca 2+ to 0.75 m m and higher induced an instantaneous contraction. However, replenishing Ca 2+ per se did not induce any contraction in the absence of bradykinin. Pretreatment with either 10 −5 m 1‐(β‐(3‐(4‐methoxyphenyl)propoxy)‐4‐methoxyphenethyl)‐1 H ‐imidazole hydrochloride (SKF96365) or 0.2 m m Ni 2+ abolished the contraction induced by bradykinin in the presence of extracellular Ca 2+ . 4 Treatment with 10 −5 m indomethacin completely inhibited the contractile response induced by Ca 2+ replenishment, regardless of the timing of its application, before or after the application of bradykinin. 5 In endothelial cells in the valvular strips, bradykinin caused a transient [Ca 2+ ] i elevation in the presence of 1.25 m m extracellular Ca 2+ , but [Ca 2+ ] i returned to the resting level within 10 min. Neither 10 −5 m SKF96365 nor 0.2 m m Ni 2+ had any effect on the peak [Ca 2+ ] i elevation, but decreased [Ca 2+ ] i in the declining phase. In the absence of extracellular Ca 2+ , bradykinin induced a transient [Ca 2+ ] i elevation to a level similar to that seen in the presence of 1.25 m m extracellular Ca 2+ . However, [Ca 2+ ] i then rapidly returned to the prestimulation level within 5 min. Subsequent Ca 2+ replenishment to 0.75 m m and higher in the presence of bradykinin elevated [Ca 2+ ] i to significantly higher levels than the resting level seen in the media containing 1.25 m m Ca 2+ . 6 In conclusion, Ca 2+ influx in the endothelial cells is essential for bradykinin to induce endothelium‐dependent contraction in the porcine interlobar renal artery.