Role of peroxynitrite in the process of vascular tone by nitric oxide and prostanoids - a nanotechnological approach

The production of peroxynitrite (ONOO-) in the endothelium decreases NO bioavailability, decreases vasorelaxation and changes vascular tone. ONOO- can also influence the production of prostacyclin-another vasorelaxant. We used a nanotechnological approach (nanosensors) to elucidate the release of NO, O-2(-), and ONOO- in endothelium and their effect on production of prostanoids. The basal ONOO- concentration near the endothelium (3-5 mum) varied from 1 to 50 nmol/L and maximal calcium ionophore stimulated ONOO-, did not exceed 900 nmol/L. The highest ONOO- concentrations were produced in ischemia/reperfusion atherosclerosis, diabetes, aging and vary among different racial groups (higher in Blacks than in Whites). ONOO- decreased PGI(2) activity with IC50 approximate to 150 nmol/L for 8 min reaction time. but has no effect of short reaction time. Prostaglandin E-1 decreased NO, O-2(-), and ONOO- by limiting Ca2+ flux into endothelium. decreased edema and vasoconstriction during ischemia/reperfusion. In endothelium (HUVEC's) of Black's the ONOO- concentrations were high 750 +/- 50 nmol/L while the lowest concentrations of vasorelaxants were 275 +/- 25 nmol/L of NO, 150 +/- 15 pb/100 mug protein of 6-keto-PGF(1z) as compared to White's (420 +/- 30 and 470 +/- nmol/L for ONOO- and NO respectively and 280 +/- 20 pg/100 mg protein for 6-keto-PGF(1z)). (C) 2004 Elsevier Ltd. All rights reserved.