Nitrosylhemoglobin formation after infusion of NO solutions: ESR studies in pigs.
A saturated nitric oxide (NO) solution (1.88 mM) infused i.v. in the anesthetized pig at a dose of 68 nmol/kg/min for 24 min resulted in a time-dependent increase of nitrosylhemoglobin [HbFe(II)NO] as determined by electron spin resonance (ESR), reaching a C(max) of 7.99 +/- 0.42 microM at the end of the infusion, compared to 1.13 +/- 0.42 microM before (p < 0.01). This indicates that NO i.v. is efficiently bioconserved as HbFe(II)NO (approximately 34% of the NO dose) and to a greater extent than by the oxidative pathway (approximately 24% of the NO dose), as determined by measuring plasma nitrites/nitrates (chemiluminescence) and Met-Hb (ESR analysis). When the NO infusion was stopped, HbFe(II)NO declined with a t(1/2) of 15 min, indicating that it is a stable storage form of NO, able to deliver NO distally to the site of administration. No significant differences were observed in systemic and pulmonary vascular resistances during and after NO infusion, but PO(2) showed a significant decrease 15 and 30 min after the infusion. Thus, in normoxic/physiological conditions, HbFe(II)NO does not induce significant NO-dependent vasorelaxation.
Aldini
Giancarlo
G
Istituto Chimico Farmaceutico Tossicologico, Faculty of Pharmacy, University of Milan, Viale Abruzzi 42, Milan 20131, Italy. giancarlo.angini@unimi.it
Orioli
Marica
M
Maffei Facino
Roberto
R
Giovanna Clement
Maria
M
Albertini
Mariangela
M
Mazzola
Silvia
S
Pirrone
Federica
F
Carini
Marina
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006454:Hemoglobins / Q000096:biosynthesis*; D007262:Infusions, Intravenous; D008163:Luminescent Measurements; D008297:Male; D008706:Methemoglobin / Q000378:metabolism; D009569:Nitric Oxide / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D012995:Solubility; D013552:Swine; D013696:Temperature; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology
D006454:Hemoglobins; C008657:nitrosyl hemoglobin; D009569:Nitric Oxide; D008706:Methemoglobin