Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension.
In this study we analyzed the role of vascular NAD(P)H oxidase in the generation of O(2)(-) and the endothelial impairment of NO signal transduction pathway in hypertension. In aortic rings of 15-month-old stroke-prone spontaneously hypertensive rats (SHR15) we found a 10-fold increased expression of NAD(P)H oxidase subunit gp91phox mRNA associated with a 3-fold increased production of O(2)(-) compared to age-matched Wistar rats (WIS15). Vasorelaxation studies in aortas of SHR15 showed a strongly diminished response to acetylcholine, NO-donor S-nitroso-N-acetyl-d,l-penicillamine, and organic nitrate glyceryl trinitrate compared to WIS15. Soluble guanylate cyclase (sGC) activity and sGC beta(1)-subunit protein expression was downregulated in aortas and lungs of SHR15. These data suggest an upregulation of vascular NAD(P)H oxidase and an impairment of the NO signal transduction pathway in hypertension.
Morawietz
H
H
Institute of Pathophysiology, Martin Luther University Halle-Wittenberg, Halle, Germany.
Weber
M
M
Rueckschloss
U
U
Lauer
N
N
Hacker
A
A
Kojda
G
G
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D015153:Blotting, Western; D004789:Enzyme Activation / Q000187:drug effects; D006162:Guanylate Cyclase / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D021122:Protein Subunits; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D008562:Membrane Glycoproteins; D020030:Nitric Oxide Donors; D021122:Protein Subunits; D012333:RNA, Messenger; D014665:Vasodilator Agents; D013481:Superoxides; D009569:Nitric Oxide; D009247:NADH, NADPH Oxidoreductases; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D006162:Guanylate Cyclase