title: The mechanism of bradykinin-induced endothelium-dependent contraction and relaxation in the porcine interlobar renal artery.
abstract: 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 (>3x10(-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(Omega)-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. 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.
authors.affiliation: Department of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 Japan.
authors.forename: E
authors.initials: E
authors.lastname: Ihara
authors.forename: K
authors.initials: K
authors.lastname: Hirano
authors.forename: D N
authors.initials: DN
authors.lastname: Derkach
authors.forename: J
authors.initials: J
authors.lastname: Nishimura
authors.forename: H
authors.initials: H
authors.lastname: Nawata
authors.forename: H
authors.initials: H
authors.lastname: Kanaide
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D005470:Fluorometry; D016257:Fura-2; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D011463:Prostaglandins H / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012077:Renal Artery / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D013928:Thromboxane A2 / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
chemical_list: D001685:Biological Factors; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D044244:Receptors, Thromboxane A2, Prostaglandin H2; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D013928:Thromboxane A2; D013930:Thromboxane-A Synthase; D001920:Bradykinin; D002118:Calcium; D016257:Fura-2