Rapid dilation of the abdominal aorta during infusion of angiotensin II detected by noninvasive high-frequency ultrasonography.

摘要

BACKGROUND: Infusion of angiotensin II (AngII) via subcutaneous osmotic pumps into mice promotes the development of abdominal aortic aneurysms (AAAs). These AngII-induced AAAs develop via a complex process in which there is a transmedial break, lumen dilation, thrombus formation, inflammation involving cells of both the innate and acquired immune systems, and remodeling. The recent development of a high-frequency ultrasound machine has permitted the noninvasive detection of murine abdominal aortas. We assessed the ability of a Visualsonics Vevo 660 high-resolution imaging system to detect AAAs and sequentially quantify the aortic luminal diameter. This system had 100% accuracy in detecting AngII-induced AAAs in vivo, with intrauser and interuser variation coefficients of less than 10% for quantification of the aortic lumen diameter. METHODS: Male apolipoprotein E (apoE)(-/-) mice were infused subcutaneously with either saline or AngII and were monitored with this ultrasonic system to define the temporal changes in aortic lumen diameter. Aortic luminal diameters were measured in the aneurysm-susceptible region of the suprarenal aorta. For internal controls, abdominal aortic diameters were measured at the level of the left renal branch, because this landmark region did not dilate during AngII infusion. RESULTS: Luminal diameters of the suprarenal aorta did not change significantly in saline-infused mice over 28 days of measurement (P = .71). In contrast, AngII infusion led to rapid dilation of suprarenal aortas during the initial 7 days of infusion (0.071 mm/d; P = .0037 for the change in the initial expansion rate). Further luminal diameter expansions occurred for the remaining 21 days of observation at a more modest rate (0.023 mm/d; P = .0001 for continued expansion after day 7). Within the initial 14 days of AngII infusion, some apoE(-/-) mice died as a result of rupture of the aorta in the suprarenal region. We had previously assumed that aortic dilation and rupture occurred simultaneously. However, in the AngII-infused mice that succumbed to aortic rupture, luminal diameters increased several days before death. CONCLUSIONS: High-frequency ultrasonography demonstrated that suprarenal aortic expansion occurs rapidly after the initiation of AngII infusion into apoE(-/-) mice.