Abstract 3663: Characterization of Cerebrovascular Parameters using MRI in Endothelial Nitric Oxide Synthase Knockout Mice
Endothelial-derived nitric oxide (NO) is important for properly regulating vascular tone and maintaining blood pressure. Mice lacking endothelial NO synthase (eNOS), i.e. loss of endothelial NO production, have systemic hypertension and develop larger cerebral infarction upon cerebral ischemia. Given that constitutively produced NO is necessary for a normal endothelial function, we posit that cerebrovascular characters in eNOS KO mice brain may differ in structure and physiology. In this study, we aim to establish MRI-derived vascular parameters such as cerebral blood volume (CBV), water exchange index (WEI), and vessel size index (VSI) using two different MRI intravascular contrast agents (Gd-PGC (Protected graft copolymer bearing covalently linked Gd- DTPA residues) and SPION (superparamagnetic iron oxide nanoparticle)). We also investigated whether perivascular aquaporine (AQP) proteins, which play a central role in the pathophysiology of many diseases, are differently expressed in eNOS KO mice. Flip angle dependence of the MRI signal intensity on transvascular water exchange rate was used to quantify CBV and WEI before and after intravenous administration of Gd-PGC using wild type mice (C57BL/6, n=8) and eNOS KO mice (n=5). 2D T2 and T2* maps were also acquired before and after SPION administration for measurements of cerebral VSI. As results, eNOS KO mice have lower VSI than that that in wild type mice (Fig. A). The CBV of eNOS KO mice is not significantly different from that of wild type mice (Fig. B). Furthermore, baseline WEI significantly increased in the eNOS KO mice, indicating higher BBB water permeability. However, both AQP1 and AQP4 were less expressed in eNOS KO mice than those in wild type mice (Fig. D). These suggest that the loss of eNOS contribute to the decrease of the vessel diameter and increase of water permeability under a baseline physiological condition. However, expression of AQP proteins forming vascular water channels is not involved with the observed water exchange rate increase across the BBB in eNOS KO mice. The study warrants future investigations to elucidate the relationship between NO synthase and the BBB integrity and its involvement with ischemic damage.
- © 2012 by American Heart Association, Inc.