Endothelial NO-Synthase Intron 4 Polymorphism is Associated with Disturbed In Vivo Nitric Oxide Production in Individuals Prone to Type 2 Diabetes

Abstract. Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease. It was hypothesized that differences in the capacity to increase glomerular filtration (functional renal reserve) would exist between these racial groups in relation to nitric oxide availability. Patients with type 2 diabetes of African-Asian (n = 9) and white (n = 9) origin with microalbuminuria were studied under euglycemic conditions. Glomerular filtration, renal plasma flow, and clearance of the stable metabolites of nitric oxide, nitrite, and nitrate were measured before and after a renal vasodilatory stimulus of a mixed amino acid intravenous infusion. There were no significant differences in age, duration of diabetes, and baseline glomerular filtration (57.1 [14.1] versus 55.8 [10.1] yr; P = 0.82, 14.5 [10.2] versus 9.1 [7.0] yr; P = 0.19 and 125.9 [30.9] versus 127.2 [44.6] ml/min per 1.73 m2; P = 0.94) between the African-Asian and white groups. Functional renal reserve, change in renal plasma flow, and percentage change in nitrate and nitrite clearance was significantly higher in the white compared with the African-Asian group (21.9 [45.7] versus -2.5 [28.2] ml/min per 1.73 m2; P = 0.043, 155.8 [205.9] versus -90.1 [146.0]; P = 0.03 ml/min per 1.73m2 and 26.7 [85.1] versus -44.7 [16.9] %; P = 0.013, respectively). The differences in functional reserve were not confounded after adjustment for diabetes duration (P = 0.034). The data suggest that these patients with type 2 diabetes of African and Asian origin lose functional renal reserve earlier in the evolution of nephropathy than whites. The differences appear to be due to defective nitric oxide production or bioavailability and might explain some of the propensity to develop end-stage renal disease.

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Effects of Periodic Body Acceleration on the In Vivo Vasoactive Response to N-w-nitro–L-arginine and the In Vitro Nitric Oxide Production

Annals of Biomedical Engineering ◽

10.1114/1.1623486 ◽

2003 ◽

Vol 31 (11) ◽

pp. 1337-1346 ◽

Cited By ~ 28

Author(s):

Jose A. Adams ◽

James E. Moore, Jr. ◽

Michael R. Moreno ◽

Jaqueline Coelho ◽

Jorge Bassuk ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Production ◽

Body Acceleration ◽

Oxide Production

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Modulation of in vivo alloreactivity by inhibition of inducible nitric oxide synthase.

Journal of Experimental Medicine ◽

10.1084/jem.181.1.63 ◽

1995 ◽

Vol 181 (1) ◽

pp. 63-70 ◽

Cited By ~ 158

Author(s):

N K Worrall ◽

W D Lazenby ◽

T P Misko ◽

T S Lin ◽

C P Rodi ◽

...

Keyword(s):

Nitric Oxide ◽

Immune Response ◽

Nitric Oxide Synthase ◽

Inducible Nitric Oxide Synthase ◽

Biologically Active ◽

Nitric Oxide Production ◽

Oxide Production ◽

Oxide Synthase ◽

Inducible Nitric Oxide

The role of nitric oxide in the immune response to allogeneic tissue was explored in an in vivo cardiac transplant model in the rat. Nitric oxide production during organ rejection was demonstrated by elevations in systemic serum nitrite/nitrate levels and by electron paramagnetic resonance spectroscopy. Messenger RNA for the inducible nitric oxide synthase enzyme was detected in the rejecting allografted heart, but not in the nonrejecting isografted heart. The enzyme was demonstrated to be biologically active by the in vitro conversion of L-arginine to L-citrulline and was immunohistochemically localized to the infiltrating inflammatory cells. Treatment with aminoguanidine, a preferential inhibitor of the inducible nitric oxide synthase isoform, prevented the increased nitric oxide production in the transplanted organ and significantly attenuated the pathogenesis of acute rejection. Aminoguanidine treatment prolonged graft survival, improved graft contractile function, and significantly reduced the histologic grade of rejection. These results suggest an important role for nitric oxide in mediating the immune response to allogeneic tissue. Inhibition of inducible nitric oxide synthase may provide a novel therapeutic modality in the management of acute transplant rejection and of other immune-mediated processes.

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Dithiocarbamate spin traps for in vivo detection of nitric oxide production in mice

Bioradicals Detected by ESR Spectroscopy ◽

10.1007/978-3-0348-9059-5_12 ◽

1995 ◽

pp. 163-171 ◽

Cited By ~ 4

Author(s):

C.-S. Lai ◽

A. M. Komarov

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Production ◽

Spin Traps ◽

Oxide Production ◽

In Vivo Detection

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Bioflavonoid-Induced Apoptosis and DNA Damage in Amastigotes and Promastigotes of Leishmania donovani: Deciphering the Mode of Action

Molecules ◽

10.3390/molecules26195843 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5843

Author(s):

Shaila Mehwish ◽

Sanjay Varikuti ◽

Mubarak Ali Khan ◽

Tariq Khan ◽

Imdad Ullah Khan ◽

...

Keyword(s):

Nitric Oxide ◽

Dna Damage ◽

Leishmania Donovani ◽

Genetic Material ◽

Mechanisms Of Action ◽

Pcr Analysis ◽

Nitric Oxide Production ◽

Oxide Production ◽

Ic50 Values

Natural products from plants contain many interesting biomolecules. Among them, quercetin (Q), gallic acid (GA), and rutin (R) all have well-reported antileishmanial activity; however, their exact mechanisms of action are still not known. The current study is a step forward towards unveil the possible modes of action of these compounds against Leishmania donovani (the causative agent of visceral leishmaniasis). The selected compounds were checked for their mechanisms of action against L. donovani using different biological assays including apoptosis and necrosis evaluation, effects on genetic material (DNA), quantitative testing of nitric oxide production, ultrastructural modification via transmission electron microscopy, and real-time PCR analysis. The results confirmed that these compounds are active against L. donovani, with IC50 values of 84.65 µg/mL, 86 µg/mL, and 98 µg/mL for Q, GA, and R, respectively. These compounds increased nitric oxide production and caused apoptosis and DNA damage, which led to changes in the treated cells’ ultrastructural behavior and finally to the death of L. donovani. These compounds also suppressed essential enzymes like trypanothione reductase and trypanothione synthetase, which are critical for leishmanial survival. The selected compounds have high antileishmanial potentials, and thus in-vivo testing and further screening are highly recommended.

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