Functional expression of kinin B1 and B2 receptors in mouse abdominal aorta

Abstract

Previous studies have shown that the vascular reactivity of the mouse aorta differs substantially from that of the rat aorta in response to several agonists such as angiotensin II, endothelin-1 and isoproterenol. However, no information is available about the agonists bradykinin (BK) and DesArg 9 BK (DBK). Our aim was to determine the potential expression of kinin B 1 and B 2 receptors in the abdominal mouse aorta isolated from C57BL/6 mice. Contraction and relaxation responses to BK and DBK were investigated using isometric recordings. The kinins were unable to induce relaxation but concentrationcontraction response curves were obtained by applying increasing concentrations of the agonists BK and DBK. These effects were blocked by the antagonists Icatibant and R-715, respectively. The potency (pD 2 ) calculated from the curves was 7.0 ± 0.1 for BK and 7.3 ± 0.2 for DBK. The efficacy was 51 ± 2% for BK and 30 ± 1% for DBK when compared to 1 µM norepinephrine. The concentration-dependent responses of BK and DBK were markedly inhibited by the arachidonic acid inhibitor indomethacin (1 µM), suggesting a mediation by the cyclooxygenase pathway. These contractile responses were not potentiated in the presence of the NOS inhibitor L-NAME (1 mM) or endothelium-denuded aorta, indicating that the NO pathway is not involved. We conclude that the mouse aorta constitutively contains B 1 and B 2 subtypes of kinin receptors and that stimulation with BK and DBK induces contractile effect mediated by endothelium-independent vasoconstrictor prostanoids.

The Role of Inflammation and COX-Derived Prostanoids in the Effects of Bradykinin on Isolated Rat Aorta and Urinary Bladder

“…It was shown that the B 1 receptor agonist causes endothelium-dependent vasodilatation through NO production in aortic rings [39]. It was also reported that the mouse aorta contains B 1 and B 2 receptors and that stimulation with BK and B 1 agonist induces vasoconstriction mediated by endothelium-independent vasoconstrictor prostanoids [40]. In another study, it was suggested that the B 1 receptors become markedly expressed in the absence of B 2 receptors and cause vasodilatation by inhibiting a vasoconstricting product of arachidonic acid cascade via the PGH 2 /TXA 2 receptor [41].…”

Deficiency or inhibition of lysophosphatidic acid receptor 1 protects against hyperoxia-induced lung injury in neonatal rats

“…, Felipe et al . , Japp & Newby ). Because we observed transient RVH in LPAR1‐deficient rats on day 10, but not in adult rats, which cannot be explained by pulmonary hypertension, we investigated whether RVH could be explained by a delayed adaptation of the foetal circulation directly after birth by studying relatively late closure of the ductus arteriosus.…”

Cellular Changes Induced by Kinin B1 Receptor Deletion: Study of Endothelial Nitric Oxide Metabolism

“…Therefore, B 1 receptor expression occurs in primary cultured endothelial cells even in the absence of inflammatory stimuli. In agreement, constitutive expression of the B 1 receptor subtype has been shown in vascular tissues of different species, including bovine aortic and pulmonary artery endothelial cells (Wiemer and Wirth 1992;Smith et al 1995;Ignjatovic et al 2002) and abdominal aorta of mice (Felipe et al 2007). The observation that the kinin B 1 -subtype is not restricted to the inflammatory context might clarify unrevealed aspects of this receptor in the vascular physiology.…”