AT1 receptor antagonist combats oxidative stress and restores nitric oxide signaling in the SHR

Abstract Adrenal steroidogenesis is modulated by humoral and neuronal factors and blood flow. Angiotensin II (AII) stimulates adrenal cortical aldosterone and cortisol production and medullary catecholamine release. However, AII regulation of adrenal vascular tone has not been characterized. We examined the effect of AII on diameters of cannulated bovine adrenal cortical arteries. Cortical arteries (average internal diameter = 230 μm) were constricted with U46619 and concentration-diameter responses to AII (10−13 to 10−8 mol/liter) were measured. In endothelium-intact arteries, AII induced dilations at low concentrations (maximum dilation = 25 ± 6% at 10−10 mol/liter) and constrictions at high concentrations (maximum constriction = 25 ± 18% at 10−8 mol/liter). AII constrictions were blocked by the angiotensin type 1 (AT1) receptor antagonist, losartan (10−6 mol/liter). AII dilations were enhanced by losartan (maximal dilation = 48 ± 8%), abolished by endothelial cell removal or N-nitro-l-arginine (L-NA, 3 × 10−5 mol/liter) and inhibited by the angiotensin type 2 (AT2) receptor antagonist, PD123319 (10−6 mol/liter, maximal dilation = 18 ± 4%). In a 4,5-diaminofluorescein diacetate nitric oxide (NO) assay of isolated cortical arteries, AII stimulated NO production, which was abolished by PD123319, L-NA, or endothelial cell removal. Western immunoblot of arterial homogenates and endothelial and zona glomerulosa cell lysates revealed 48-kD and 50-kD bands corresponding to AT1 and AT2 receptors, respectively, in all three and a 140-kD band corresponding to endothelial NO synthase in endothelial cells and arteries. Our results demonstrate that AII stimulates adrenal cortical arterial dilation through endothelial cell AT2 receptor activation and NO release and AT1 receptor-dependent constriction.

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The role of nitric oxide signaling in renoprotective effects of hydrogen sulfide against chronic kidney disease in rats: Involvement of oxidative stress, autophagy and apoptosis

Journal of Cellular Physiology ◽

10.1002/jcp.27797 ◽

2018 ◽

Vol 234 (7) ◽

pp. 11411-11423 ◽

Cited By ~ 7

Author(s):

Mohammad Khabbaz Shirazi ◽

Asaad Azarnezhad ◽

Mohammad Foad Abazari ◽

Mansour Poorebrahim ◽

Pegah Ghoraeian ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Chronic Kidney Disease ◽

Hydrogen Sulfide ◽

Kidney Disease ◽

Nitric Oxide Signaling

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Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe

Nitric Oxide ◽

10.1016/j.niox.2015.11.001 ◽

2016 ◽

Vol 52 ◽

pp. 29-40 ◽

Cited By ~ 19

Author(s):

Rika Indri Astuti ◽

Daisuke Watanabe ◽

Hiroshi Takagi

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Stress Response ◽

Schizosaccharomyces Pombe ◽

Oxidative Stress Response ◽

Nitric Oxide Signaling

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Improvement of endothelial dysfunction in experimental heart failure by chronic RAAS-blockade: ACE-inhibition or AT1-receptor blockade?

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/14703203010020011101 ◽

2001 ◽

Vol 2 (1_suppl) ◽

pp. S64-S69 ◽

Cited By ~ 1

Author(s):

Lodewijk J Wagenaar ◽

Hendrik Buikema ◽

Yigal M Pinto ◽

Wiek H van Gilst

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Heart Failure ◽

Endothelial Dysfunction ◽

Endothelial Function ◽

Candesartan Cilexetil ◽

Ace Inhibition ◽

At1 Receptor ◽

Converting Enzyme Inhibitors ◽

Raas Blockade

Chronic heart failure (CHF) is associated with endothelial dysfunction. Activation of the renin-angiotensin-aldosterone system (RAAS) is believed to be important in the deterioration of endothelial dysfunction in CHF through stimulation of oxidative stress. Whereas angiotensin-converting enzyme inhibitors (ACE-I) improve endothelial function in CHF, the effects of angiotensin II AT1-receptor blockers (ARB) are less well established. Therefore we compared the effects of the ACE-I lisinopril vs. the ARB candesartan on endothelial dysfunction in a rat model of CHF. CHF was induced by myocardial infarction (MI) after coronary ligation. Two weeks after MI, daily treatment with lisinopril (2 mg/kg) or candesartan cilexetil (1.5 mg/kg) was started. After 13 weeks, rats were sacrificed and endothelial function was determined by measuring acetylcholine (ACh)-induced vasodilation in aortic rings, with selective presence of the nitric oxide synthase (NOS)-inhibitor NG-monomethyl-L-arginine (L-NMMA) to determine the contribution of nitric oxide (NO). ACh-induced vasodilation was attenuated in untreated MI (-50%) compared with control rats. This was in part due to an impaired contribution of NO (-49%). Lisinopril and candesartan cilexetil fully normalised ACh-induced dilation, including the part mediated by NO. Chronic RAAS-blockade with lisinopril and candesartan cilexetil normalised endothelial function in CHF in a comparable way. The effect of both treatments included the increase of the NO-mediated dilation, further indicating the important role of oxidative stress in the relationship between the RAAS and endothelial dysfunction in CHF.

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Oxidative stress and nitric oxide signaling related biomarkers in patients with pulmonary hypertension: a case control study

BMC Pulmonary Medicine ◽

10.1186/s12890-015-0045-8 ◽

2015 ◽

Vol 15 (1) ◽

Cited By ~ 23

Author(s):

Shuai Zhang ◽

Ting Yang ◽

Xiaomao Xu ◽

Meng Wang ◽

Linye Zhong ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Pulmonary Hypertension ◽

Case Control Study ◽

Case Control ◽

Nitric Oxide Signaling ◽

Control Study

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Protein nitration as footprint of oxidative stress-related nitric oxide signaling pathways in developing Ciona intestinalis

Nitric Oxide ◽

10.1016/j.niox.2012.03.012 ◽

2012 ◽

Vol 27 (1) ◽

pp. 18-24 ◽

Cited By ~ 9

Author(s):

Elena Ercolesi ◽

Gabriella Tedeschi ◽

Gabriella Fiore ◽

Armando Negri ◽

Elisa Maffioli ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Signaling Pathways ◽

Ciona Intestinalis ◽

Protein Nitration ◽

Nitric Oxide Signaling

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Nitric Oxide Signaling Is Disrupted in the Yeast Model for Batten Disease

Molecular Biology of the Cell ◽

10.1091/mbc.e06-11-1053 ◽

2007 ◽

Vol 18 (7) ◽

pp. 2755-2767 ◽

Cited By ~ 47

Author(s):

Nuno S. Osório ◽

Agostinho Carvalho ◽

Agostinho J. Almeida ◽

Sérgio Padilla-Lopez ◽

Cecília Leão ◽

...

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Batten Disease ◽

Cell Types ◽

Neuronal Ceroid Lipofuscinoses ◽

Juvenile Form ◽

Nitric Oxide Signaling ◽

Induced Apoptosis ◽

And Oxidative Stress ◽

Yeast Model

The juvenile form of neuronal ceroid lipofuscinoses (JNCLs), or Batten disease, results from mutations in the CLN3 gene, and it is characterized by the accumulation of lipopigments in the lysosomes of several cell types and by extensive neuronal death. We report that the yeast model for JNCL (btn1-Δ) that lacks BTN1, the homologue to human CLN3, has increased resistance to menadione-generated oxidative stress. Expression of human CLN3 complemented the btn1-Δ phenotype, and equivalent Btn1p/Cln3 mutations correlated with JNCL severity. We show that the previously reported decreased levels of l-arginine in btn1-Δ limit the synthesis of nitric oxide (·NO) in both physiological and oxidative stress conditions. This defect in ·NO synthesis seems to suppress the signaling required for yeast menadione-induced apoptosis, thus explaining btn1-Δ phenotype of increased resistance. We propose that in JNCL, a limited capacity to synthesize ·NO directly caused by the absence of Cln3 function may contribute to the pathology of the disease.

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