Effect of beta-blockers on endothelial function during biological aging: a nanotechnological approach.
Biological aging is an independent risk factor for many cardiovascular diseases; some are treated with beta-blockers that may protect dysfunctional endothelium during aging by increasing NO, decreasing ONOO, and restoring NO/ONOO balance. A nanotechnological approach was used to simultaneously monitor NO and ONOO produced by a single aortic endothelial cell from Wistar-Kyoto rats of different ages. beta-blockers (metoprolol and atenolol) were administered 2 weeks before the animals were sacrificed. Nanosensors were placed near the endothelium, and calcium ionophore- stimulated NO and ONOO release was measured. Endothelial nitric oxide synthase (eNOS) undergoes uncoupling with aging, manifested by a decrease in NO (from 503 +/- 12 to 163 +/- 5 nmol/L) and a 3-fold increase in ONOO for 16-week-old and 110- week- old rats, respectively. Metoprolol reversed eNOS uncoupling, increased the production rate and concentration of NO, and increased an overall ratio of NO]/ONOO]. This effect was not observed with atenolol, but L-arginine, sepiapterin, and superoxide dismutase were beneficial.
Funovic
Philip
P
Department of orthopaedics, Medical University of Vienna, Vienna, Austria.
Korda
Mykhaylo
M
Kubant
Ruslan
R
Barlag
Rebecca E
RE
Jacob
Robert F
RF
Mason
R Preston
RP
Malinski
Tadeusz
T
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging / Q000502:physiology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D001120:Arginine / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D016922:Cellular Senescence / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008790:Metoprolol / Q000494:pharmacology; D036103:Nanotechnology; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D011622:Pterins / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D011622:Pterins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D001262:Atenolol; D001120:Arginine; C016727:sepiapterin; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D008790:Metoprolol