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 m arked up-regulations of endothelial nitric oxide synthase (eNOS) in heart a nd thoracic aorta and of neuronal NOS (nNOS) in the brain of rats with seve re aortic coarctation above the renal arteries. We hypothesize that the pre sence of severe regional HTN in the face of marked up-regulation of NO syst em 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 wit h ROS) was determined by Western blot in sham-operated control and aortic-b anded (above renal arteries) rats three weeks postoperatively. Intra-arteri al pressure and tissue nitrotyrosine (Western blot) were measured. Results. The banded group showed a marked rise in arterial pressure measure d 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 b lood pressure was not elevated. Conclusion. Coarctation-induced HTN is associated with increased nitrotyros ine abundance in all tissues exposed to high arterial pressure, denoting en hanced ROS-mediated inactivation and sequestration of NO in these sites. Th is can, in part, account for severe regional HTN in this model. The normali ty of nitrotyrosine abundance in the abdominal aorta wherein blood pressure is not elevated points to the role of baromechanical factors as opposed to circulating Immoral factors that were necessarily similar in both segments .