The mechanism of bradykinin-induced endothelium-dependent contraction and relaxation in the porcine interlobar renal artery

Eikichi Ihara, Katsuya Hirano, Dmitry N. Derkach, Junji Nishimura, Hajime Nawata, Hideo Kanaide

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28 Citations (Scopus)

Abstract

1. The mechanism of endothelium-dependent regulation of vascular tone of bradykinin was investigated by simultaneously monitoring the changes in the cytosolic Ca2+ concentration and the force of smooth muscle in fura-2-loaded strips of the porcine renal artery with endothelium. 2. During phenylephrine-induced sustained contraction, bradykinin (> 3 x 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. 3. At low concentrations (10-10-10-9 M), bradykinin caused an endothelium-dependent biphasic relaxation with no contraction. 4. A thromboxane A2 (TXA2)/prostaglandin H2 (PGH2) receptor antagonist (10-5 M ONO-3708) completely inhibited, while a TXA2 synthase inhibitor (10-5 M OKY-046) only partially inhibited, the transient contraction induced by bradykinin. 5. 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 mM 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. 6. 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 TXA2 and PGH2 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.

Original languageEnglish
Pages (from-to)943-952
Number of pages10
JournalBritish Journal of Pharmacology
Volume129
Issue number5
DOIs
Publication statusPublished - 2000

All Science Journal Classification (ASJC) codes

  • Pharmacology

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