scholarly journals Nitric Oxide and Carbon Monoxide Have a Stimulatory Role in the Hypothalamic-Pituitary-Adrenal Response to Physico-Emotional Stressors in Rats*

Endocrinology ◽  
2000 ◽  
Vol 141 (6) ◽  
pp. 2244-2253 ◽  
Author(s):  
C. Kwon Kim ◽  
Catherine L. Rivier
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Carbon Monoxide ◽  
Activity Levels ◽  
Hypothalamic Pituitary Adrenal ◽  
Adrenal Response ◽  
Nos Inhibitor ◽  
Tin Protoporphyrin ◽  
Oxide Synthase ◽  
The Brain

Abstract We tested the hypothesis that nitric oxide and carbon monoxide, which are produced in the brain by nitric oxide synthase (NOS) and heme oxygenase (HO), modulate the hypothalamic-pituitary-adrenal response to physico-emotional stressors by acting at the hypothalamus. Accordingly, we determined 1) whether the intracerebroventricular (icv) injection of NOS or HO inhibitors at doses that were confined to the brain attenuated electroshock-induced ACTH release; and 2) whether the decreases in this ACTH response were concurrent with decreases in NOS or HO activity levels at the hypothalamus. Icv injection of the NOS inhibitor Nω-nitro-l-arginine-methylester (L-NAME; 50 μg) or the HO inhibitor tin protoporphyrin (SnPP; 20–25μ g) significantly blunted the plasma ACTH response to a 45-min session of intermittent electroshocks. Importantly, in these same animals there were concurrent decreases in hypothalamic NOS or HO activities, respectively. There were little or no effects of these inhibitors on anterior pituitary NOS or HO activities, indicating that there was only minimal leakage of the drug from the brain after icv administration. The specificity of action of these inhibitors was confirmed by the fact that SnPP did not affect NOS activity, and L-NAME did not affect HO activity. Finally, L-NAME produced no effect, whereas SnPP produced only transient increases in blood pressure, suggesting that these inhibitors do not affect activity indirectly through alterations in blood pressure. These data support the hypothesis that in the whole animal, both NO and CO exert a stimulatory influence on the acute ACTH response to physico-emotional stressors, and that the hypothalamus is the critical site of their actions.

Abstract 111: Xanthine Oxidoreductase Plays a Key Role in Nitrate, Nitrite and Nitric Oxide Homeostasis When the Endothelial Nitric Oxide Synthase is Compromised

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Christa Zollbrecht ◽  
Marcelo Montenegro ◽  
Michael Hezel ◽  
Eddie Weitzberg ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Primary Source ◽  
No Production ◽  
Xanthine Oxidoreductase ◽  
Physiological Conditions ◽  
Inorganic Nitrate ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Xanthine oxidoreductase (XOR) is generally known as a source of superoxide production, but this enzyme has also been suggested to mediate NO production via reduction of inorganic nitrate (NO 3 - ) and nitrite(NO 2 - ). This pathway for NO generation is of particular importance during certain pathologies, whereas endothelial NO synthase (eNOS) is the primary source of vascular NO generation under normal physiological conditions. The exact interplay between the NOS and XOR-derived NO is not yet fully elucidated. The aim of the present study was to investigate if eNOS deficiency is partly compensated by XOR upregulation and sensitization of the NO 3 - - NO 2 - - NO pathway. NO 3 - and NO 2 - were similar between naïve eNOS KO and wildtype (wt) mice, but reduced upon chronic treatment with the non-selective NOS inhibitor L-NAME (wt: 25.0±5.2, eNOS KO: 39.2±6.4, L-NAME: 8.2±1.6 μ NO 3 - -, wt: 0.38±0.07, eNOS KO: 0.42±0.04, L-NAME: 0.12±0.02 μ NO 2 - ). XOR function was upregulated in eNOS KO compared with wt mice [(mRNA: wt 1±0.07, eNOS KO 1.38±0.17), (activity: wt 825±54, eNOS KO 1327±280 CLU/mg/min), (uric acid: wt 32.87±1.53, eNOS KO 43.23±3.54 μ)]. None of these markers of XOR activity was increased in nNOS KO and iNOS KO mice. Following acute dose of NO 3 - (10 mg/kg bw, i.p.), the increase of plasma NO 2 - was more pronounced in eNOS KO (+0.51±0.13 μ) compared with wt (+0.22±0.09 μ), and this augmented response in the eNOS KO was abolished by treatment with the highly selective XOR inhibitor febuxostat (FEB). Liver from eNOS KO had higher reducing capacity of NO 2 - to NO compared with wt, and this effect was attenuated by FEB (Δppb of NO: wt +8.7±4.2, eNOS KO +44.2±15.0, wt+FEB +22.2±9.6, eNOS KO+FEB +26.8±10.2). Treatment with FEB increased blood pressure in eNOS KO (ΔMAP:+10.2±5.6 mmHg), but had no effect in wt (ΔMAP:-0.6±3.3 mmHg). Supplementation with NO 3 - (10 mM, drinking water) reduced blood pressure in eNOS KO (ΔMAP: -6.3±2.2 mmHg), and this effect was abolished by FEB (ΔMAP: +1.1±1.9 mmHg). In conclusion, upregulated and altered XOR function in conditions with eNOS deficiency can facilitate the NO 3 - - NO 2 - - NO pathway and hence play a significant role in vascular NO homeostasis.

scholarly journals Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production

2007 ◽  
Vol 194 (1) ◽  
pp. 11-20 ◽  
Author(s):  
N Grion ◽  
E M Repetto ◽  
Y Pomeraniec ◽  
C Martinez Calejman ◽  
F Astort ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Lethal Dose ◽  
Activity Levels ◽  
Steroid Production ◽  
Signaling Systems ◽  
Adrenal Response ◽  
Oxide Synthase

The present study was designed to investigate the effect of lipopolysaccharide (LPS) on the expression levels and activities of the nitric oxide synthase (NOS) and heme oxygenase (HO) systems in the rat adrenal gland. Both enzymatic activities were significantly increased in this tissue after in vivo treatment with LPS. The concurrent induction of the HO-1, NOS-1, and NOS-2 gene products was also detected as both mRNAs and protein levels were augmented by this treatment in a time-dependent way. A significant interaction between both signaling systems was also demonstrated as in vivo blockage of NOS activity with N(G)-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in HO expression and activity levels, while an increase in NOS activity was observed when HO was inhibited by Sn-protoporphyrin IX (Sn-PPIX). As both NOS and HO activities have been previously involved in the modulation of adrenal steroidogenesis, we investigated the participation of these signaling systems in the adrenal response to LPS. Our results showed that acute stimulation of steroid production by ACTH was significantly increased when either NOS or HO activities were inhibited. We conclude that adrenal NOS and HO can be induced by a non-lethal dose of endotoxin supporting a modulatory role for these activities in the adrenal response to immune challenges.

scholarly journals Nitric oxide synthase, ADMA, SDMA, and nitric oxide activity in the paraventricular nucleus throughout the etiology of renal wrap hypertension

2012 ◽  
Vol 302 (11) ◽  
pp. H2276-H2284 ◽  
Author(s):  
Carrie A. Northcott ◽  
Scott Billecke ◽  
Teresa Craig ◽  
Carmen Hinojosa-Laborde ◽  
Kaushik P. Patel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Paraventricular Nucleus ◽  
No Synthase ◽  
Elevated Blood ◽  
Inhibitory Effects ◽  
Symmetric Dimethylarginine ◽  
Inhibitory Neurotransmitters ◽  
Nos Inhibitor ◽  
Oxide Synthase

Within the paraventricular nucleus (PVN), there is a balance between the excitatory and inhibitory neurotransmitters that regulate blood pressure; in hypertension, the balance shifts to enhanced excitation. Nitric oxide (NO) is an atypical neurotransmitter that elicits inhibitory effects on cardiovascular function. We hypothesized that reduced PVN NO led to elevations in blood pressure during both the onset and sustained phases of hypertension due to decreased NO synthase (NOS) and increased asymmetrical dimethylarginine (ADMA; an endogenous NOS inhibitor) and symmetric dimethylarginine (SDMA). Elevated blood pressure, in response to PVN bilateral microinjections of a NO inhibitor, nitro-l-arginine methyl ester, was blunted in renal wrapped rats during the onset of hypertension ( day 7) and sustained renal wrap hypertension ( day 28) compared with sham-operated rats. Adenoviruses (Ad) encoding endothelial NOS (eNOS) or LacZ microinjected into the PVN [1 × 109 plaque-forming units, bilateral (200 nl/site)] reduced mean arterial pressure compared with control ( Day 7, Ad LacZ wrap: 144 ± 7 mmHg and Ad eNOS wrap: 117 ± 5 mmHg, P ≤ 0.05) throughout the study ( Day 28, Ad LacZ wrap: 123 ± 1 mmHg and Ad eNOS wrap: 108 ± 4 mmHg, P ≤ 0.05). Western blot analyses of PVN NOS revealed significantly lower PVN neuronal NOS during the onset of hypertension but not in sustained hypertension. Reduced SDMA was found in the PVN during the onset of hypertension; however, no change in ADMA was observed. In conclusion, functional indexes of NO activity indicated an overall downregulation of NO in renal wrap hypertension, but the mechanism by which this occurs likely differs throughout the development of hypertension.

Effects of carbon monoxide on the brain may be mediated by nitric oxide

1996 ◽  
Vol 81 (3) ◽  
pp. 1078-1083 ◽  
Author(s):  
S. Meilin ◽  
G. G. Rogatsky ◽  
S. R. Thom ◽  
N. Zarchin ◽  
E. Guggenheimer-Furman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Oxidative Metabolism ◽  
Combined Treatment ◽  
Physiological Role ◽  
Low Doses ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
The Brain

Carbon monoxide (CO) is known to be a toxic molecule due to the high affinity of hemoglobin for it. However, it has recently been shown that low doses of CO may play a physiological role. The aim of the present study was to examine processes occurring in the brain during exposure to 1,000 parts per million CO that result in an increase in cerebral blood flow (CBF) but are not accompanied by changes in oxidation metabolism. This study was carried out in awake rats with the multiprobe assembly developed in this laboratory for the simultaneous continuous measurement of CBF, intramitochondrial NADH redox levels, direct current potential, and extracellular concentrations of K+, Ca2+, and H+ as well as the electrocorticogram. Exposure to 1,000 parts per million CO in air resulted in an increased CBF without any concomitant changes in any of the other metabolic or ionic parameters measured. This indicates that tissue hypoxia was not the trigger for this vasodilation. Injection of N omega-nitro-L-arginine (L-NNA), a nitric oxide synthase inhibitor, before exposure to CO effectively blocked the increase in CBF that was observed when the animal was exposed to CO without prior injection of L-NNA. Furthermore, electrocorticographic depression was observed after the combined treatment of L-NNA and CO. In conclusion, exposure to relatively low doses of CO apparently does not have a deleterious effect on oxidative metabolism because the increase in CBF after this exposure is sufficient to prevent changes in oxidative metabolism, as indicated by the fact that NADH levels remained constant. This protective autoregulatory effect may be mediated by nitric oxide.

scholarly journals Changing standard chow diet promotes vascular NOS dysfunction in Dahl S rats

2012 ◽  
Vol 302 (1) ◽  
pp. R150-R158 ◽  
Author(s):  
Frank T. Spradley ◽  
Dao H. Ho ◽  
Kyu-Tae Kang ◽  
David M. Pollock ◽  
Jennifer S. Pollock
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Methyl Ester ◽  
Mesenteric Arteries ◽  
Chow Diet ◽  
Small Arteries ◽  
Standard Chow Diet ◽  
Small Resistance ◽  
Nos Inhibitor ◽  
Oxide Synthase

We hypothesized that vascular nitric oxide synthase (NOS) function and expression is differentially regulated in adult Dahl salt-sensitive rats maintained on Teklad or American Institutes of Nutrition (AIN)-76A standard chow diets from 3 to 16 wk old. At 16 wk old, acetylcholine (ACh)-mediated vasorelaxation and phenylephrine (PE)-mediated vasoconstriction in the presence and absence of NOS inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME), was assessed in small-resistance mesenteric arteries and aortas. Rats maintained on either diet throughout the study had similar responses to ACh and PE in the presence or absence of l-NAME in both vascular preparations. We reasoned that changing from one diet to another as adults may induce vascular NOS dysfunction. In the absence of l-NAME, small arteries from Teklad-fed rats switched to AIN-76 diet and vice versa had similar responses to ACh and PE. Small-arterial NOS function was maintained in rats switched to AIN-76A from Teklad diet, whereas NOS function in response to ACh and PE was lost in the small arteries from rats changed to Teklad from AIN-76A diet. This loss of NOS function was echoed by reduced expression of NOS3, as well as phosphorylated NOS3. The change in NOS phenotype in the small arteries was observed without changes in blood pressure. Aortic responses to ACh or PE in the presence or absence of l-NAME were similar in all diet groups. These data indicate that changing standard chow diets leads to small arterial NOS dysfunction and reduced NOS signaling, predisposing Dahl salt-sensitive rats to vascular disease.

Effects of S-isopropyl isothiourea, a potent inhibitor of nitric oxide synthase, in severe hemorrhagic shock

1996 ◽  
Vol 81 (2) ◽  
pp. 707-715 ◽  
Author(s):  
A. Vromen ◽  
C. Szabo ◽  
G. J. Southan ◽  
A. L. Salzman
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Hemorrhagic Shock ◽  
Renal Perfusion ◽  
Beneficial Effects ◽  
Arterial Blood ◽  
Nos Inhibitor ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

We characterized the response to intravenous S-isopropyl isothiourea (IPTU), a novel potent nitric oxide synthase (NOS) inhibitor, in rodent and porcine models of hemorrhagic shock (HS). IPTU (at 300 micrograms/kg, administered as 3 subsequent bolus injections), in anesthetized rats hemorrhaged to a mean arterial blood pressure (MAP) of 35 mmHg, increased MAP and improved survival over 120 min. In anesthetized pigs hemorrhaged to a MAP of 45 mmHg, IPTU (0.3 mg/kg plus 1 mg.kg-1.h-1) increased MAP and systemic vascular resistance. IPTU did not alter the cardiac index, renal blood flow, arterial and portal oxygen content, or splanchnic oxygen consumption or extraction. In contrast, infusion of norepinephrine (100 micrograms.kg-1.h-1) did not alter MAP and increased mortality in the rat model, whereas it caused a transient increase in MAP and a tachycardia in the porcine model of HS without significantly affecting the other parameters studied. Inhibition of the endothelial NOS in early severe HS may have beneficial effects on blood pressure and survival without altering cardiac output and splanchnic and renal perfusion.

scholarly journals Effect of Melatonin on Blood Pressure and Nitric Oxide Generation in Rats With Metabolic Syndrome

2016 ◽  
pp. S373-S380 ◽  
Author(s):  
J. KLIMENTOVA ◽  
M. CEBOVA ◽  
A. BARTA ◽  
Z. MATUSKOVA ◽  
S. VRANKOVA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Protein Expression ◽  
Brain Cortex ◽  
Brain Regions ◽  
Melatonin Treatment ◽  
Protein Expressions ◽  
Oxide Synthase ◽  
The Brain

Melatonin, a multitasking indolamine, seems to be involved in a variety of physiological and metabolic processes via both receptor-mediated and receptor-independent mechanisms. The aim of our study was to find out whether melatonin can affect blood pressure (BP), nitric oxide synthase (NOS) activity, eNOS and nNOS protein expressions in rats with metabolic syndrome (SHR/cp). Rats were divided into four groups: 6-week-old male WKY andSHR/cp and age-matched WKY and SHR/cp treated with melatonin (10 mg/kg/day) for 3 weeks. BP was measured by tail-cuff plethysmography. NOS activity, eNOS and nNOS protein expressions were determined in the heart, aorta, brain cortex and cerebellum. MT1 receptors were analyzed in the brain cortex and cerebellum. In SHR/cp rats, BP was decreased after melatonin treatment. In the same group, melatonin did not affect NOS activity and eNOS protein expression in the heart and aorta, while it increased both parameters in the brain cortex and cerebellum. Interestingly, melatonin elevated MT1 protein expression in the cerebellum. Neuronal NOS protein expression was not changed within the groups. In conclusion, increased NOS activity/eNOS upregulation in particular brain regions may contribute partially to BP decrease in SHR/cp rats after melatonin treatment. Participation of MT1 receptors in this melatonin action may be supposed.

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