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.