Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide.
Previous work in our laboratory showed increased basal periarterial nitric oxide (NO) and H2O2 concentrations in the spontaneously hypertensive rat, characterized by oxidant stress, as well as impaired flow-mediated NO production that was corrected by a reduction of periarterial H2O2. Aging is also associated with an increase in vascular reactive oxygen species and results in abnormal vascular function. The current study was designed to assess the role of H2O2 in regulating NO production during vascular aging. In vivo, real-time NO and H2O2 concentrations were measured by microelectrodes in mesenteric arteries of retired breeder (aged; 8-12 mo) and young (2 to 3 mo) Wistar-Kyoto rats under conditions of altered flow. The results in aged rats revealed elevated basal NO (1,611+/-286 vs. 793+/-112 nM, P<0.05) and H2O2 concentrations (16+/-2 vs. 9+/-1 microM, P<0.05) and a flow-mediated increase in H2O2 but not NO production. Pretreatment of aged rats with the antioxidant apocynin lowered both basal H2O2 (8+/-1 microM) and NO (760+/-102 nM) to young levels and restored flow-mediated NO production. Similar results were obtained with the NAD(P)H oxidase inhibitor gp91ds-tat. In addition, acute incubation with topical polyethylene-glycolated catalase lowered the baseline NO concentration and restored flow-mediated NO production. Taken together, the data indicate that elevated baseline and suppressed flow-mediated NO production in aged Wistar-Kyoto rats are mediated by NAD(P)H oxidase-derived H2O2.
Department of Surgery, Indiana University School of Medicine, 1001 W. 10th St., WD OPW 425F, Indianapolis, IN 46202-2879, USA.
Xiaosun
X
Zhou
H Glenn
HG
Bohlen
Joseph L
JL
Unthank
Steven J
SJ
Miller
D000098:Acetophenones / Q000494:pharmacology; D000287:Administration, Topical; D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism*; D017736:Ion-Selective Electrodes; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology*; D008839:Microelectrodes; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D051381:Rats; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow; D013152:Splanchnic Circulation; D013997:Time Factors
D000098:Acetophenones; D000975:Antioxidants; D004791:Enzyme Inhibitors; D006023:Glycoproteins; C070295:catalase-polyethylene glycol; C473031:gp91ds-tat protein, chimeric; D009569:Nitric Oxide; D011092:Polyethylene Glycols; C056165:acetovanillone; D006861:Hydrogen Peroxide; D002374:Catalase; D019255:NADPH Oxidases