Role of peroxynitrite in the process of vascular tone regulation by nitric oxide and prostanoids—a nanotechnological approach
By Kozak, Allyson J.; Liu, Feng; Funovics, Philip; Jacoby, Adam; Kubant, Ruslan & Malinski, Tadeusz
Published in Prostaglandins, Leukotrienes and Essential Fatty Acids
2005
Abstract
Summary 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, O2-, and ONOO- in endothelium and their effect on production of prostanoids. The basal ONOO- concentration near the endothelium (3–5 μm) 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 PGI2 activity with IC50≈150 nmol/L for 8 min reaction time, but has no effect of short reaction time. Prostaglandin E1 decreased NO, O2-, 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 μg protein of 6-keto-PGF1α 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-PGF1α).