Enhanced nitric oxide inactivation in aortic coarctation-induced hypertension.
BACKGROUND
Abdominal aortic coarctation above the renal arteries leads to severe hypertension (HTN) above the stenotic site. We have recently shown marked up-regulations of endothelial nitric oxide synthase (eNOS) in heart and thoracic aorta and of neuronal NOS (nNOS) in the brain of rats with severe aortic coarctation above the renal arteries. We hypothesize that the presence of severe regional HTN in the face of marked up-regulation of NO system may be partly due to enhanced NO inactivation by reactive oxygen species (ROS) leading to functional NO deficiency.


METHODS
Tissue nitrotyrosine (which is the footprint of NO interaction with ROS) was determined by Western blot in sham-operated control and aortic-banded (above renal arteries) rats three weeks postoperatively. Intra-arterial pressure and tissue nitrotyrosine (Western blot) were measured.


RESULTS
The banded group showed a marked rise in arterial pressure measured directly through a carotid cannula (203 +/- 9 vs. 131 +/- 2 mm Hg, P < 0.01). Compared with the sham-operated controls, the banded animals exhibited significant increases in nitrotyrosine abundance in the heart, brain, and the aorta segment above the stricture. In contrast, nitrotyrosine abundance was unchanged in the abdominal aorta segment below the stricture wherein blood pressure was not elevated.


CONCLUSIONS
Coarctation-induced HTN is associated with increased nitrotyrosine abundance in all tissues exposed to high arterial pressure, denoting enhanced ROS-mediated inactivation and sequestration of NO in these sites. This can, in part, account for severe regional HTN in this model. The normality of nitrotyrosine abundance in the abdominal aorta wherein blood pressure is not elevated points to the role of baromechanical factors as opposed to circulating humoral factors that were necessarily similar in both segments.
Barton
C H
CH
Division of Nephrology and Hypertension, Department of Medicine, University of California, Irvine, California, USA.
Ni
Z
Z
Vaziri
N D
ND
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism; D001013:Aorta, Thoracic / Q000378:metabolism; D001017:Aortic Coarctation / Q000150:complications*; D017704:Baroreflex; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis
D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine