Noninvasive Imaging of Angiogenesis Inhibition Following Nitric Oxide Synthase Blockade in the Ischemic Rat Heart in Vivo

Abstract

Nitric oxide synthase inhibition has anti-angiogenic properties. Magnetic resonance (MR) imaging was used to image the functional significance of these microvascular changes in a rat model of chronic ischemic myocardium in vivo. The authors quantitatively determined myocardial perfusion and regional blood volume, left ventricular geometry, and function using MR imaging. Animals received either L-NAME + hydralazine or no treatment and were investigated 1 and 2 weeks after induction of coronary artery stenosis or sham operation at rest and during vasodilatation. Double-labeling immunohistochemistry was used to visualize angiogenesis and to compare with data obtained by MR imaging. Left ventricular mass and end-diastolic volumes were comparable in both groups 2 weeks after treatment. However, basal and maximum perfusion in animals with L-NAME + hydralazine treatment were reduced compared to animals not treated (p < .05). Basal regional blood volume remained constant in all groups, whereas maximum regional blood volume was reduced by L-NAME + hydralazine (p < .05). Endothelial cell proliferation, a direct marker for angiogenesis, was reduced by L-NAME + hydralazine (p < .01). MR imaging allows noninvasive quantification of functional microcirculation and angiogenesis in the rat heart in vivo. Nitric oxide synthase blockade results in changes in functional microcirculation and in an inhibition of angiogenesis in both ischemic and nonischemic myocardial tissue.