0460 : Nitric oxide and hemoglobin form a paramagnetic compound quantifiable by Electron Paramagnetic Resonance (EPR) spectroscopy in venous erythrocytes that reflects vascular NO bioavailability in vivo

Background In senescent heart, beta-adrenergic response is altered in parallel with beta1- and beta2-adrenoceptor down-regulation. A negative inotropic effect of beta3-adrenoceptor could be involved. In this study, the authors tested the hypothesis that beta3-adrenoceptor plays a role in beta-adrenergic dysfunction in senescent heart. Methods beta-Adrenergic responses were investigated in vivo (echocardiography-dobutamine, electron paramagnetic resonance) and in vitro (isolated left ventricular papillary muscle, electron paramagnetic resonance) in young adult (3-month-old) and senescent (24-month-old) rats. Nitric oxide synthase (NOS) immunolabeling (confocal microscopy), nitric oxide production (electron paramagnetic resonance) and beta-adrenoceptor Western blots were performed in vitro. Data are mean percentages of baseline +/- SD. Results An impaired positive inotropic effect (isoproterenol) was confirmed in senescent hearts in vivo (117 +/- 23 vs. 162 +/- 16%; P < 0.05) and in vitro (127 +/- 10 vs. 179 +/- 15%; P < 0.05). In the young adult group, the positive inotropic effect was not significantly modified by the nonselective NOS inhibitor N-nitro-L-arginine methylester (L-NAME; 183 +/- 19%), the selective NOS1 inhibitor vinyl-L-N-5(1-imino-3-butenyl)-L-ornithine (L-VNIO; 172 +/- 13%), or the selective NOS2 inhibitor 1400W (183 +/- 19%). In the senescent group, in parallel with beta3-adrenoceptor up-regulation and increased nitric oxide production, the positive inotropic effect was partially restored by L-NAME (151 +/- 8%; P < 0.05) and L-VNIO (149 +/- 7%; P < 0.05) but not by 1400W (132 +/- 11%; not significant). The positive inotropic effect induced by dibutyryl-cyclic adenosine monophosphate was decreased in the senescent group with the specific beta3-adrenoceptor agonist BRL 37344 (167 +/- 10 vs. 142 +/- 10%; P < 0.05). NOS1 and NOS2 were significantly up-regulated in the senescent rat. Conclusions In senescent cardiomyopathy, beta3-adrenoceptor overexpression plays an important role in the altered beta-adrenergic response via induction of NOS1-nitric oxide.

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Detection of angiotensin II mediated nitric oxide release within the nucleus of the solitary tract using electron-paramagnetic resonance (EPR) spectroscopy

Autonomic Neuroscience ◽

10.1016/j.autneu.2006.02.016 ◽

2006 ◽

Vol 126-127 ◽

pp. 193-201 ◽

Cited By ~ 24

Author(s):

J.F.R. Paton ◽

T. Lonergan ◽

J. Deuchars ◽

P.E. James ◽

S. Kasparov

Keyword(s):

Nitric Oxide ◽

Electron Paramagnetic Resonance ◽

Angiotensin Ii ◽

Epr Spectroscopy ◽

Solitary Tract ◽

Paramagnetic Resonance ◽

Nitric Oxide Release ◽

Electron Paramagnetic

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SU-C-BRD-05: Non-Invasive in Vivo Biodosimetry in Radiotherapy Patients Using Electron Paramagnetic Resonance (EPR) Spectroscopy

Medical Physics ◽

10.1118/1.4923800 ◽

2015 ◽

Vol 42 (6Part2) ◽

pp. 3192-3193 ◽

Cited By ~ 5

Author(s):

N Bahar ◽

K Roberts ◽

F Stabile ◽

N Mongillo ◽

RD Decker ◽

...

Keyword(s):

Electron Paramagnetic Resonance ◽

Epr Spectroscopy ◽

Paramagnetic Resonance ◽

Non Invasive ◽

Electron Paramagnetic

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Applications of in vivo electron paramagnetic resonance (EPR) spectroscopy: measurements of pO2 and NO in endotoxin shock

Toxicology Letters ◽

10.1016/s0378-4274(01)00277-6 ◽

2001 ◽

Vol 120 (1-3) ◽

pp. 253-257 ◽

Cited By ~ 10

Author(s):

Simon K. Jackson ◽

Melanie Madhani ◽

Matthew Thomas ◽

Graham S. Timmins ◽

Philip E. James

Keyword(s):

Electron Paramagnetic Resonance ◽

Epr Spectroscopy ◽

Endotoxin Shock ◽

Paramagnetic Resonance ◽

Electron Paramagnetic

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In Vivo Formation of Electron Paramagnetic Resonance-Detectable Nitric Oxide and of Nitrotyrosine Is Not Impaired during Murine Leishmaniasis

Infection and Immunity ◽

10.1128/iai.66.2.807-814.1998 ◽

1998 ◽

Vol 66 (2) ◽

pp. 807-814 ◽

Cited By ~ 41

Author(s):

Selma Giorgio ◽

Edlaine Linares ◽

Harry Ischiropoulos ◽

Fernando José Von Zuben ◽

Aureo Yamada ◽

...

Keyword(s):

Nitric Oxide ◽

Electron Paramagnetic Resonance ◽

Parasite Burden ◽

Immunohistochemical Analysis ◽

Mouse Strains ◽

No Production ◽

Cutaneous Lesions ◽

Paramagnetic Resonance ◽

Electron Paramagnetic

ABSTRACT Recent studies have provided evidence for a dual role of nitric oxide (NO) during murine leishmaniasis. To explore this problem, we monitored the formation of NO and its derived oxidants during the course of Leishmania amazonensis infection in tissues of susceptible (BALB/c) and relatively resistant (C57BL/6) mice. NO production was detected directly by low-temperature electron paramagnetic resonance spectra of animal tissues. Both mouse strains presented detectable levels of hemoglobin nitrosyl (HbNO) complexes and of heme nitrosyl and iron-dithiol-dinitrosyl complexes in the blood and footpad lesions, respectively. Estimation of the nitrosyl complex levels demonstrated that most of the NO is synthesized in the footpad lesions. In agreement, immunohistochemical analysis of the lesions demonstrated the presence of nitrotyrosine in proteins of macrophage vacuoles and parasites. Since macrophages lack myeloperoxidase, peroxynitrite is likely to be the nitrating NO metabolite produced during the infection. The levels of HbNO complexes in the blood reflected changes occurring during the infection such as those in parasite burden and lesion size. The maximum levels of HbNO complexes detected in the blood of susceptible mice were higher than those of C57BL/6 mice but occurred at late stages of infection and were accompanied by the presence of bacteria in the cutaneous lesions. The results indicate that the local production of NO is an important mechanism for the elimination of parasites if it occurs before the parasite burden becomes too high. From then on, elevated production of NO and derived oxidants aggravates the inflammatory process with the occurrence of a hypoxic environment that may favor secondary infections.

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