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

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.