| First Author | Agbor LN | Year | 2011 |
| Journal | Biochem Pharmacol | Volume | 82 |
| Issue | 5 | Pages | 514-23 |
| PubMed ID | 21684261 | Mgi Jnum | J:175457 |
| Mgi Id | MGI:5285766 | Doi | 10.1016/j.bcp.2011.06.011 |
| Citation | Agbor LN, et al. (2011) Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness. Biochem Pharmacol 82(5):514-23 |
| abstractText | Hypotension in aryl hydrocarbon receptor knockout mice (ahr(-/-)) is mediated, in part, by a reduced contribution of angiotensin (Ang) II to basal blood pressure (BP). Since AHR is highly expressed in endothelial cells (EC), we hypothesized that EC-specific ahr(-/-) (ECahr(-/-)) mice would exhibit a similar phenotype. We generated ECahr(-/-) mice by crossing AHR floxed mice (ahr(fx/fx)) to mice expressing Cre recombinase driven by an EC-specific promoter. BP was assessed by radiotelemetry prior to and following an acute injection of Ang II or chronic treatment with an angiotensin converting enzyme inhibitor (ACEi). ECahr(-/-) mice were hypotensive (ECahr(+/+): 116.1+/-1.4; ECahr(-/-): 107.4+/-2.0 mmHg, n=11, p<0.05) and exhibited significantly different responses to Ang II and ACEi. While Ang II increased BP in both genotypes, the increase was sustained in ECahr(+/+), whereas the increase in ECahr(-/-) mice steadily declined. Area under the curve analysis showed that Ang II-induced increase in diastolic BP (DBP) over 30 min was significantly lower in ECahr(-/-) mice (ECahr(+/+) 1297+/-223 mmHg/30 min; ECahr(-/-)(AUC): 504+/-138 mmHg/30 min, p<0.05). In contrast, while ACEi decreased BP in both genotypes, the subsequent rise in DBP after treatment was significantly delayed in the ECahr(-/-) mice. ECahr(-/-) mice also exhibited reduced vascular and adipose Ang II type 1 receptor (AT1R) expression, and reduced aortic Ang II-dependent vasoconstriction in the presence of vascular adipose. Taken together these data suggest that hypotension in ECahr(-/-) mice results from reduced vascular responsiveness to Ang II that is influenced by AT1R expression and adipose. |
