Chronic high pressure-induced arterial oxidative stress: involvement of protein kinase C-dependent NAD(P)H oxidase and local renin-angiotensin system.
Regardless of the underlying pathological mechanisms oxidative stress seems to be present in all forms of hypertension. Thus, we tested the hypothesis that chronic presence of high pressure itself elicits increased arterial O(2)(.-) production. Hypertension was induced in rats by abdominal aortic banding (Ab). Rats with Ab had elevated pressure in vessels proximal and normal pressure in vessels distal to the coarctation, yet both vascular beds were exposed to the same circulating factors. Compared to normotensive hind limb arteries (HLAs) hypertensive forelimb arteries (FLAs) exhibited 1) impaired dilations to acetylcholine and the nitric oxide donor S-nitroso-N-acetyl-D,L-penicillamine that were restored by administration of superoxide dismutase; 2) an increased production of O(2)(.-) (measured by lucigenin chemiluminescence and ethidium bromide fluorescence) that was inhibited or reduced by superoxide dismutase, the NAD(P)H oxidase inhibitors diphenyleneiodonium and apocynin, or the protein kinase C (PKC) inhibitors chelerythrine and staurosporine or by the angiotensin-converting enzyme (ACE) inhibitor captopril; and 3) increased ACE activity. In organ culture, exposure of isolated arteries of normotensive rats to high pressure (160 mmHg, for 24 hours) significantly increased O(2)(.-) production compared to that in arteries exposed to 80 mmHg. High pressure-induced O(2)(.-) generation was reduced by inhibitors of ACE and PKC. Incubation of cultured arteries with angiotensin II elicited significantly increased O(2)(.-) generation that was inhibited by chelerythrine. Thus, we propose that chronic presence of high pressure itself can elicit arterial oxidative stress, primarily by activating directly a PKC-dependent NAD(P)H oxidase pathway, but also, in part, via activation of the local renin-angiotensin system.
Ungvari
Zoltan
Z
Department of Physiology, Basic Sciences Building, New York Medical College, Valhalla, NY 10595, USA.
Csiszar
Anna
A
Kaminski
Pawel M
PM
Wolin
Michael S
MS
Koller
Akos
A
D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000470:Alkaloids; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D053119:Benzophenanthridines; D002216:Captopril / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D008954:Models, Biological; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D009861:Onium Compounds / Q000494:pharmacology; D009924:Organ Culture Techniques; D018384:Oxidative Stress; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012084:Renin-Angiotensin System / Q000187:drug effects*; D019311:Staurosporine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000098:Acetophenones; D000470:Alkaloids; D000806:Angiotensin-Converting Enzyme Inhibitors; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009861:Onium Compounds; D010617:Phenanthridines; C110881:S-nitro-N-acetylpenicillamine; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; C007517:diphenyleneiodonium; D002216:Captopril; C056165:acetovanillone; C016299:chelerythrine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D011493:Protein Kinase C; D010396:Penicillamine; D019311:Staurosporine; D000109:Acetylcholine