Different Prostanoids Are Involved in Bradykinin-Induced Endothelium-Dependent and -Independent Vasoconstriction in Rat Mesenteric Resistance Arteries

Abstract

Abstract. Mechanisms underlying bradykinin-induced vasoconstriction were investigated in rat perfused mesenteric vascular beds with active tone. In preparations with intact endothelium, bolus injections of bradykinin (1 to 1,000 pmol) dose-dependently produced three-phase vascular effects, which consisted of a first-phase vasodilation followed by a second-phase vasoconstriction and a subsequent third-phase vasodilation; these effects were abolished by FR172357 (bradykinin B 2 -receptor antagonist), but not by des-Arg 9 -[Leu 8 ]-bradykinin (bradykinin B 1 -receptor antagonist). In preparations with intact endothelium, indomethacin (cyclooxygenase inhibitor), seratrodast (thromboxane A 2 (TXA 2 )-receptor antagonist), ONO-3708 (TXA 2 / prostaglandin H 2 (PGH 2 )-receptor antagonist) or ozagrel (TXA 2 synthesis inhibitor) markedly inhibited the bradykinin-induced vasoconstriction. In preparations without endothelium, the bradykinin-induced vasoconstriction was abolished by indomethacin and ONO-3708, while seratrodast and ozagrel had no effect. These results suggest that the endothelium-dependent vasoconstriction of bradykinin is mainly mediated by TXA 2 and that prostanoids other than TXA 2 , probably PGH 2 , in mesenteric vascular smooth muscle are responsible for bradykinin-induced endothelium-independent vasoconstriction.

Flow enhances the agonist-induced responses of the bradykinin receptor (B2) because of its lectinic nature: Role of its oligosaccharide environment

“…In addition, the amplitude of the contractile responses of the vascular smooth muscle is a direct indicator of endothelial paracrine signaling [20][21][22][23][24][25]. This preparation constitutes a system more similar to an in vivo model, making it a suitable agile system for quantitative studies on the mechanisms of flow-activation of endothelial surface layer endothelial processes with changes in vascular smooth muscle contraction serving as an [20][21][22][23][24][25].…”

“…An isolated blood vessel preparation was selected because it is a simple anatomical model and frequently used to study functional interactions between endothelial and adjacent smooth muscle cells [16][17][18][19][20][21][22][23][24][25]. For our study we chose the isolated guinea pig carotid artery which has an internal diameter of about 0.5 mm, a length of 1.5 ± 0.5 cm and can be perfused at a controlled flow.…”

“…Intravascular bradykinin acts exclusively and selectively by activation of bradykinin B2 receptors in the endothelial surface layer [36]. Although bradykinin-induced vasodilation is frequently reported, in the guinea pig carotid artery as well other blood vessels, the response is a receptor-mediated constriction [19][20][21][22][23][24][25]. This vasoconstriction response was blocked by Hoe 140, a specific bradykinin B2 receptor antagonist (not shown) [37].…”

“…L-NAME (L-N 6 -nitroarginine methyl ester), an analog of arginine that inhibits nitric oxide production, is expected to potentiate the bradykinin concentration-constrictor response curves because the dilation is prevented [19][20][21][22][23][24][25]35]. As described for group 1, control dose-response curves to bradykinin were obtained at 11 and16 ml/min.…”

“…Bradykinin is an agonist capable of causing vasodilation, vasoconstriction or both, and, although vasodilation is commonly reported, vasoconstriction occurs in various vascular preparations [19][20][21][22][23][24][25]45]. To illustrate the vasoconstriction response at different concentrations of bradykinin, original recordings are shown in figure 1.…”