| First Author | Bergaya S | Year | 2004 |
| Journal | Circ Res | Volume | 94 |
| Issue | 12 | Pages | 1623-9 |
| PubMed ID | 15131008 | Mgi Jnum | J:100063 |
| Mgi Id | MGI:3586438 | Doi | 10.1161/01.RES.0000131497.73744.1a |
| Citation | Bergaya S, et al. (2004) Flow-dependent dilation mediated by endogenous kinins requires angiotensin AT2 receptors. Circ Res 94(12):1623-9 |
| abstractText | The vascular kallikrein-kinin system contributes to about one third of flow-dependent dilation in mice carotid arteries, by activating bradykinin B2 receptors coupled to endothelial nitric oxide (NO) release. Because the bradykinin/NO pathway may mediate some of the effects of angiotensin II AT2 receptors, we examined the possible contribution of AT2 receptors to the kinin-dependent response to flow. Changes in outer diameter after increases in flow rate were evaluated in perfused arteries from wild-type animals (TK+/+) and in tissue kallikrein-deficient mice (TK-/-) in which the presence of AT2 receptor expression was verified. Saralasin, a nonselective angiotensin II receptor antagonist, impaired significantly flow-induced dilation in TK+/+, whereas it had no effect in TK-/- mice. In both groups, blockade of AT1 receptors with losartan or candesartan did not affect the response to flow. Inhibition of AT2 receptors with PD123319 reduced significantly flow-induced dilation in TK+/+ mice, but had no significant effect in TK-/- mice. Combining PD123319 with the bradykinin B2 receptor antagonist HOE-140 had no additional effect to AT2 receptor blockade alone in TK+/+ arteries. Flow-dependent-dilation was also impaired in AT2 receptor deficient mice (AT2-/-) when compared with wild-type littermates. Furthermore, HOE-140 significantly reduced the response to flow in the AT2+/+, but not in AT2-/- mice. In conclusion, this study demonstrates that the presence of functional AT2 receptors is necessary to observe the contribution of the vascular kinin-kallikrein system to flow-dependent dilation. |
