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The mechanism of bradykinin‐induced endothelium‐dependent contraction and relaxation in the porcine interlobar renal artery
Author(s) -
Ihara Eikichi,
Hirano Katsuya,
Derkach Dmitry N,
Nishimura Junji,
Nawata Hajime,
Kanaide Hideo
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703141
Subject(s) - bradykinin , contraction (grammar) , phenylephrine , medicine , endocrinology , chemistry , endothelium , thromboxane a2 , prostaglandin , receptor , blood pressure
The mechanism of endothelium‐dependent regulation of vascular tone of bradykinin was investigated by simultaneously monitoring the changes in the cytosolic Ca 2+ concentration and the force of smooth muscle in fura‐2‐loaded strips of the porcine renal artery with endothelium. During phenylephrine‐induced sustained contraction, bradykinin (>3×10 −9 M ) caused endothelium‐dependent triphasic changes in the force of the strips, composed of an initial relaxation, a subsequent transient contraction and a late sustained relaxation. At low concentrations (10 −10 –10 −9 M ), bradykinin caused an endothelium‐dependent biphasic relaxation with no contraction. A thromboxane A 2 (TXA 2 )/prostaglandin H 2 (PGH 2 ) receptor antagonist (10 −5 M ONO‐3708) completely inhibited, while a TXA 2 synthase inhibitor (10 −5 M OKY‐046) only partially inhibited, the transient contraction induced by bradykinin. Under conditions where the bradykinin‐induced contraction was inhibited by ONO‐3708 during the phenylephrine‐induced contraction, bradykinin induced only a transient relaxation in the presence of N Ω ‐nitro‐ L ‐arginine methyl ester ( L ‐NAME). This transient relaxation was inhibited when the precontraction was initiated by phenylephrine plus 40 m M extracellular K + . The removal of L ‐NAME from this condition caused a partial reappearance of the initial relaxation and a complete reappearance of the sustained relaxation. In conclusion, bradykinin caused the endothelium‐dependent triphasic regulation of vascular tone in the porcine renal artery. The concentrations of bradykinin required to induce a contraction was higher than that required to induce relaxation. Both TXA 2 and PGH 2 were involved in the bradykinin‐induced contraction. The initial relaxation was mediated by nitric oxide and hyperpolarizing factors while the sustained relaxation depended on nitric oxide.British Journal of Pharmacology (2000) 129 , 943–952; doi: 10.1038/sj.bjp.0703141