Bradykinin‐induced oedema formation proceeds from B₂ receptor stimulation and is potentiated by concomitantly released prostaglandins

Abstract

Bradykinin, a stimulator of B1 and B2 receptors, significantly increased PGI2 synthesis and fluid extravasation, as assessed by the increase of organ weight when injected intraarterially into the artificially perfused rabbit hindquarters preparation. Diclofenac pretreatment prevented PGI2 synthesis and significantly reduced fluid extravasation. Oedema formation and PGI2 synthesis were also significantly reduced by a simultaneous infusion of papaverine. Selective stimulation of B1-type receptors with des-Arg9-bradykinin was not accompanied by edema formation nor PGI2 synthesis but by a significant rise in vascular resistance. The combined application of bradykinin and the selective B1 receptor antagonist des-Arg9-[Leu8]-bradykinin also resulted in oedema formation and PGI2 synthesis, the extent, however, being significantly reduced in comparison to the application of bradykinin only. The data suggest that bradykinin-induced oedema proceeds from B2 receptor stimulation and is potentiated by simultaneous stimulation of B1 receptors. The kinin-induced fluid extravasation seems to be augmented by concomitantly generated prostaglandins.

Influence of B2 receptor antagonists on bradykinin-induced vasodilation and edema formation in isolated rabbit hindlimbs

“…1, 2). These results are well consistent with previous studies, indicating the major role of B 2 receptors in mediating these vascular effects of bradykinin [2,18,19].…”

Antinociceptive Effect of a Novel Tosylpyrazole Compound in Mice

“…An interesting finding was the lack of anti‐oedematogenic effect of celecoxib in bradykinin‐induced oedema, at a dose where it reduced the oedema caused by carrageenan. It has been extensively demonstrated that non‐selective cyclooxygenase inhibitors reduce the oedema caused by bradykinin [33]. Our results suggest that such effect is mediated by cyclooxygenase‐1, but not by cyclooxygenase‐2, since celecoxib was devoid of effect in bradykinin‐induced oedema.…”

The role of insulin as an antithrombotic humoral factor

“…(30)(31)(32) In 1993, we provided the first report that insulin at physiologic amounts stimulated the synthesis of the prostanoid in endothelial cells. (33) 3.…”

“…Although prostacyclin is known to be one of the most potent inhibitors of platelet aggregation and is synthesized from arachidonate in endothelial cells, (30) the regulatory mechanism involved in the synthesis of prostanoid under physiologic conditions remains poorly understood, although some of the stimulators of prostacyclin synthesis under pathologic conditions have been reported. (30)(31)(32) In 1993, we provided the first report that insulin at physiologic amounts stimulated the synthesis of the prostanoid in endothelial cells. (33) 3.…”