Role of peroxynitrite in the process of vascular tone regulation 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 microm) 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 IC(50) approximately 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 Ca(2+) 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 microg protein of 6-keto-PGF(1)(alpha) 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(1)(alpha)).
Kozak
Allyson J
AJ
Department of Chemistry and Biochemistry, Ohio University, 350 West State Street, Athens, OH 45701, USA.
Liu
Feng
F
Funovics
Philip
P
Jacoby
Adam
A
Kubant
Ruslan
R
Malinski
Tadeusz
T
D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D011464:Epoprostenol / Q000037:antagonists & inhibitors; D006801:Humans; D007511:Ischemia / Q000378:metabolism; D008297:Male; D036103:Nanotechnology / Q000379:methods; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D030421:Peroxynitrous Acid / Q000032:analysis / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D044469:Racial Groups; D051381:Rats; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology; D014664:Vasodilation
D011453:Prostaglandins; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D000527:Alprostadil