Intraluminal pressure increases vascular neuronal nitric oxide synthase expression

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Abstract
Development of high blood pressure (BP) is associated with an increased expression of neuronal nitric oxide synthase (nNOS) in vascular smooth muscle cells. We investigated whether or not changes in intraluminal pressure affect nNOS expression in carotid arteries of normotensive rats. Expression of nNOS and other NOS isoforms was determined by Western blot analysis in rat carotid arteries maintained up to 24 h at different levels of intraluminal pressure in an organ culture system. Expression of nNOS in arteries exposed to 80 mmHg was stable for the duration of the experiment. Increasing intraluminal pressure to 200 mmHg transiently augmented nNOS expression at 9 h, both in intact arteries and in arteries where the endothelium and the adventitia were removed. The expression of endothelial NOS (eNOS) was also augmented under similar experimental conditions, but only after 24 h exposure. The ERK1/2 kinase cascade inhibitor PD 98059 significantly impaired the expression of nNOS in arteries exposed to 200 mmHg for 9 h. However, the angiotensin AT1 antagonist candesartan and the angiotensin converting enzyme inhibitor perindoprilat did not have any effect under the same experimental conditions. Finally, the preferential nNOS inhibitor S-methyl-L-thiocitrulline significantly augmented the contraction evoked by angiotensin II in arteries exposed to 200 mmHg, but not in those maintained at 80 mmHg intraluminal pressure for 9 h. These results show that transmural pressure increases nNOS expression and NO release in rat smooth muscle cells by a mechanism involving the mitogen-activated protein kinase pathway, but independent from the local formation of angiotensin II.