Noninvasive imaging of angiogenesis inhibition following nitric oxide synthase blockade in the ischemic rat heart in vivo.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Waller
Christiane
C
Medizinische Universitätsklinik, Würzburg, Germany. waller_c@medizin.uni-wuerzburg.de
Hiller
Karl-Heinz
KH
Rüdiger
Thomas
T
Kraus
Günter
G
Konietzko
Christian
C
Hardt
Nelly
N
Ertl
Georg
G
Bauer
Wolfgang Rudolf
WR
D000818:Animals; D049109:Cell Proliferation; D004730:Endothelium, Vascular; D005260:Female; D006334:Heart Function Tests; D008279:Magnetic Resonance Imaging; D008833:Microcirculation / Q000187:drug effects; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester