Calcitonin Gene-Related Peptide Protects Against Cardiovascular Dysfunction Independently of Nitric Oxide In Vivo

The neuropeptide CGRP (calcitonin gene-related peptide) is a potent vasodilator, with a cardioprotective role, although the precise mechanisms are unclear. Here we show the ability of endogenous and exogenous CGRP to restore blood pressure, when nitric oxide synthesis is blocked, in a model of cardiovascular disease associated with endothelial dysfunction and impaired nitric oxide production. Male wild-type and αCGRP knockout mice received L-nitro-arginine methyl ester (150 mg/kg in drinking water) to induce a sustained hypertension with evidence of cardiovascular remodeling. The hypertensive response was exacerbated in L-nitro-arginine methyl ester-treated αCGRP knockouts, indicating that endogenous αCGRP acts in a protective manner, when nitric oxide production is diminished. Exogenous CGRP rescued αCGRP knockout mice from both hypertension and cardiovascular remodeling. Further studies using a nonrecovery protocol with a CGRP receptor antagonist (BIBN4096 BS) revealed that CGRP acts via the canonical CGRP receptor (CLR [calcitonin-like receptor]/RAMP1 [receptor activity-modifying protein]); with no effect of an antagonist (AC187) of a second CGRP-responsive receptor (the amylin-1 receptor, CTR [calcitonin receptor]/RAMP1). Blood flow, in resistance vessels of the exteriorised mesentery, was investigated. Noradrenaline–induced vasoconstriction with recovery, in L-nitro-arginine methyl ester-treated wild-type mice. However, αCGRP knockout, or BIBN4096 BS-treated wild-type mice demonstrated a similar constrictor response to noradrenaline, but significantly impaired blood flow recovery. The combined findings highlight that αCGRP protects against cardiovascular dysfunction, signaling via the canonical CGRP receptor and acting when nitric oxide production is lost, such as in endothelial dysfunction associated with vascular disease. These in vivo results support the proposal that CGRP provides a novel treatment for cardiovascular 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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Regulation of cerebellar nitric oxide production in response to prolonged in vivo hypoxia

Journal of Neuroscience Research ◽

10.1002/(sici)1097-4547(19970701)49:1<89::aid-jnr10>3.0.co;2-# ◽

1997 ◽

Vol 49 (1) ◽

pp. 89-97 ◽

Cited By ~ 42

Author(s):

Yang Guo ◽

Michael E. Ward ◽

Stephan Beasjours ◽

Masataka Mori ◽

Sabah N.A. Hussain

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Production ◽

Oxide Production

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Adenosine Modulates N -Methyl- d -Aspartate–Stimulated Hippocampal Nitric Oxide Production In Vivo

Stroke ◽

10.1161/01.str.26.9.1627 ◽

1995 ◽

Vol 26 (9) ◽

pp. 1627-1633 ◽

Cited By ~ 31

Author(s):

Anish Bhardwaj ◽

Frances J. Northington ◽

Raymond C. Koehler ◽

Theodore Stiefel ◽

Daniel F. Hanley ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Production ◽

Oxide Production

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Viral mutation accelerated by nitric oxide production during infection in vivo

The FASEB Journal ◽

10.1096/fasebj.14.10.1447 ◽

2000 ◽

Vol 14 (10) ◽

pp. 1447-1454 ◽

Cited By ~ 14

Author(s):

Takaaki Akaike ◽

Shigemoto Fujii ◽

Atsushi Kato ◽

Jun Yoshitake ◽

Yoichi Miyamoto ◽

...

Keyword(s):

Nitric Oxide ◽

Nitric Oxide Production ◽

Oxide Production ◽

Viral Mutation

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The 12-HHT/BLT2/NO Axis Is Associated to the Wound Healing and Skin Condition in Different Glycaemic States

Medical Sciences ◽

10.3390/medsci7040065 ◽

2019 ◽

Vol 7 (4) ◽

pp. 65

Author(s):

Leguina-Ruzzi ◽

Ortiz Diban ◽

Velarde

Keyword(s):

Nitric Oxide ◽

Wound Healing ◽

Tight Junction ◽

Skin Condition ◽

Inos Mrna ◽

Nitric Oxide Production ◽

Mrna Levels ◽

Oxide Production

Type 2 diabetes affects over 340 million people worldwide. This condition can go unnoticed and undiagnosed for years, leading to a late stage where high glycaemia produces complications such as delayed wound healing. Studies have shown that 12-HHT through BLT2, accelerates keratinocyte migration and wound healing. Additionally, evidence has shown the role of nitric oxide as a pro-regenerative mediator, which is decreased in diabetes. Our main goal was to study the association between the 12-HHT/BLT2 axis and the nitric oxide production in wound healing under different glycaemia conditions. For that purpose, we used in vivo and in vitro models. Our results show that the skin from diabetic mice showed reduced BLT2 and iNOS mRNA, TEER, 12-HHT, nitrites, and tight junction levels, accompanied by higher MMP9 mRNA levels. Furthermore, a positive correlation between BLT2 mRNA and nitrites was observed. In vitro, HaCaT-BLT2 cells showed higher nitric oxide and tight junction levels, and reduced MMP9 mRNA levels, compared to mock-keratinocytes under low and high glucose condition. The wound healing capacity was associated with higher nitric oxide production and was affected by the NOS inhibition. We suggest that the BLT2 expression improves the keratinocyte response to hyperglycaemia, associated with the production of nitric oxide.

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A Dirofilaria immitis Polyprotein Up-Regulates Nitric Oxide Production

Infection and Immunity ◽

10.1128/iai.70.9.5283-5286.2002 ◽

2002 ◽

Vol 70 (9) ◽

pp. 5283-5286 ◽

Cited By ~ 9

Author(s):

Hiroyuki Tezuka ◽

Shinjiro Imai ◽

Setsuko Tsukidate ◽

Koichiro Fujita

Keyword(s):

Nitric Oxide ◽

Dirofilaria Immitis ◽

Peritoneal Macrophages ◽

No Production ◽

Nitric Oxide Production ◽

Wild Type ◽

Murine Macrophages ◽

Oxide Production

ABSTRACT We investigated the effect of recombinant Dirofilaria immitis polyprotein (rDiAg) on nitric oxide (NO) production by peritoneal macrophages. rDiAg induced NO production by macrophages from wild-type and lipopolysaccharide-hyporesponsive C3H/HeJ, but not CD40−/−, mice. These results suggest that CD40 is involved in rDiAg-driven NO production by murine macrophages.

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