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This Article Full Text Full Text (PDF) All Versions of this Article: 294/1/H183    most recent 01040.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Macarthur, H. Articles by Wilken, G. H. Search for Related Content PubMed PubMed Citation Articles by Macarthur, H. Articles by Wilken, G. H.

Oxidative stress attenuates NO-induced modulation of sympathetic neurotransmission in the mesenteric arterial bed of spontaneously hypertensive rats

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri

Submitted 7 September 2007 ; accepted in final form 21 October 2007

Current evidence suggests that hyperactivity of the sympathetic nervous system and endothelial dysfunction are important factors in the development and maintenance of hypertension. Under normal conditions the endothelial mediator nitric oxide (NO) negatively modulates the activity of the norepinephrine portion of sympathetic neurotransmission, thereby placing a "brake" on the vasoconstrictor ability of this transmitter. This property of NO is diminished in the isolated, perfused mesenteric arterial bed taken from the spontaneously hypertensive rat (SHR), resulting in greater nerve-stimulated norepinephrine and lower neuropeptide Y (NPY) overflow from this mesenteric preparation compared with that of the normotensive Wistar-Kyoto rat (WKY). We hypothesized that increased oxidative stress in the SHR contributes to the dysfunction in the NO modulation of sympathetic neurotransmission. Here we demonstrate that the antioxidant N-acetylcysteine reduced nerve-stimulated norepinephrine and increased NPY overflow in the mesenteric arterial bed taken from the SHR. Furthermore, this property of N-acetylcysteine was prevented by inhibiting nitric oxide synthase with N-nitro-L-arginine methyl ester, demonstrating that the effect of N-acetylcysteine was due to the preservation of NO from oxidation. Despite a reduction in norepinephrine overflow, the nerve-stimulated perfusion pressure response in the SHR mesenteric bed was not altered by the inclusion of N-acetylcysteine. Studies including the Y₁ antagonist BIBO 3304 with N-acetylcysteine demonstrated that this preservation of the perfusion pressure response was due to elevated NPY overflow. These results demonstrate that the reduction in the bioavailability of NO as a result of elevated oxidative stress contributes to the increase in norepinephrine overflow from the SHR mesenteric sympathetic neuroeffector junction.

antioxidant; hypertension; nitric oxide; norepinephrine; neuropeptide Y

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