Effect of NO Synthase Blockade on Myocardial Contractility of Hypokinetic Rats during Stimulation of β-Adrenoreceptors

2016 ◽  
Vol 161 (2) ◽  
pp. 215-217 ◽  
Author(s):  
R. I. Zaripova ◽  
N. I. Ziyatdinova ◽  
T. L. Zefirov
Keyword(s):  
Myocardial Contractility ◽  
No Synthase ◽  
Stimulation Of

SOME ASPECTS OF MECHANISM OF SUCCINAMIDES INFLUENCE ON METABOLIC HOMEOSTASIS OF THE ORGANISM

2018 ◽  
pp. 27-31
Author(s):  
I. A. Palagina
Keyword(s):  
Nitric Oxide ◽  
Biological Activity ◽  
Antioxidant System ◽  
No Synthase ◽  
Antioxidant Potential ◽  
Metabolic Homeostasis ◽  
Energetic Metabolism ◽  
Complex Action ◽  
Energy Processes ◽  
Stimulation Of

Succinate containing compounds possess many types of biological activity and are used for the development of drugs with the target and complex action. This paper is devoted to some aspects of the mechanism of succinamides’ action in a dose of 100 mg/kg. We studied the influence of the compound with antidiabetic properties, -phenylethylamide of 2-oxysuccinanyl acid ( -PhEA-OSAA), and its metabolites such as 2-hydroxyphenylsuccinamide (2-HPhSA) and β-phenylethylsuccinamide ( -PhESA) on the marker indicators of energetic metabolism (EM), antioxidant system (AOS) and nitric oxide (NO) metabolism in subacute experiment on rats. Studies have shown that the action of -FEA-OSAKA on metabolic homeostasis is realized through stimulation of EM, reduction of intensity of NO-synthase metabolism and weakening of the AOS. The nature of the action of -FES and 2-GFS, taking into account the indicators of the state of homeostasis, largely coincides with β-FEA-OSAKA. It was found that the key links in the mechanism of toxic action of succinamides are the effect on antioxidant potential, NO metabolism and energy processes.

scholarly journals Dexamethasone increased the survival rate in Plasmodium berghei-infected mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danilo Reymão Moreira ◽  
Ana Carolina Musa Gonçalves Uberti ◽  
Antonio Rafael Quadros Gomes ◽  
Michelli Erica Souza Ferreira ◽  
Aline da Silva Barbosa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Survival Rate ◽  
Plasmodium Berghei ◽  
Redox Status ◽  
No Synthase ◽  
Ischemia And Reperfusion ◽  
Inos Inhibition ◽  
The Brain ◽  
Plasmodial Infection ◽  
Stimulation Of

AbstractThe present study aimed to evaluate the effects of dexamethasone on the redox status, parasitemia evolution, and survival rate of Plasmodium berghei-infected mice. Two-hundred and twenty-five mice were infected with Plasmodium berghei and subjected to stimulation or inhibition of NO synthesis. The stimulation of NO synthesis was performed through the administration of L-arginine, while its inhibition was made by the administration of dexamethasone. Inducible NO synthase (iNOS) inhibition by dexamethasone promoted an increase in the survival rate of P. berghei-infected mice, and the data suggested the participation of oxidative stress in the brain as a result of plasmodial infection, as well as the inhibition of brain NO synthesis, which promoted the survival rate of almost 90% of the animals until the 15th day of infection, with possible direct interference of ischemia and reperfusion syndrome, as seen by increased levels of uric acid. Inhibition of brain iNOS by dexamethasone caused a decrease in parasitemia and increased the survival rate of infected animals, suggesting that NO synthesis may stimulate a series of compensatory redox effects that, if overstimulated, may be responsible for the onset of severe forms of malaria.

On the Respective Roles of Nitric Oxide and Carbon Monoxide in Long-Term Potentiation in the Hippocampus

1999 ◽  
Vol 6 (1) ◽  
pp. 63-76 ◽  
Author(s):  
Min Zhuo ◽  
Jarmo T. Laitinen ◽  
Xiao-Ching Li ◽  
Robert D. Hawkins
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Guanylyl Cyclase ◽  
Hippocampal Slices ◽  
Long Term Potentiation ◽  
No Synthase ◽  
Term Potentiation ◽  
Stimulation Of

Perfusion of hippocampal slices with an inhibitor nitric oxide (NO) synthase blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.

Nitric oxide and penile erection in streptozotocin-diabetic rats

1999 ◽  
Vol 96 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Gil ARI ◽  
Yoram VARDI ◽  
John P. M. FINBERG
Keyword(s):  
Methyl Ester ◽  
Time Course ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
No Synthase ◽  
Sprague Dawley ◽  
Nerve Roots ◽  
Sprague Dawley Rats ◽  
Pithed Rats ◽  
Stimulation Of

The purpose of this investigation was to study the time course, response to insulin and characteristics of erectile dysfunction in streptozotocin (STZ)-diabetic Sprague–Dawley rats, and the function of the NO-generating system in these animals. Copulation-induced and reflex erection were quantified in conscious Sprague–Dawley rats at different times after injection of STZ. The corporal vasodilatation response to nerve stimulation was studied by measuring the rise in corporal pressure in pithed rats following electrical stimulation of sacral spinal nerve roots. The activity of NO synthase was determined in corporal tissue by measuring the generation of [3H]citrulline from [3H]arginine. Copulation-induced erection was inhibited at 1 and 2 months after STZ treatment, but this could be prevented by a short (2-week) pretreatment with insulin. Reflex erection was inhibited at 1, 4, 6 and 9 months after STZ; at 6 months, this inhibition was also reversible by insulin pretreatment. Following pithing, the basal corporal pressure was elevated in diabetic rats. At 4 months after STZ, this increase was normalized by a 2-week, but not by a 1-week, pretreatment with insulin; however, at 9 months after STZ, insulin pretreatment did not normalize corporal pressure. The increase in corporal pressure caused by stimulation of sacral nerve roots in pithed rats was enhanced in diabetic animals. This enhancement was also normalized at 4 months, but not at 9 months, by 2 weeks of insulin treatment. The inhibition of the stimulation-induced increase in corporal pressure by NG-nitro-L-arginine methyl ester (5 mg/kg) was less following 9 months of diabetes, although NO synthase activity was normal in cavernosal tissue following 6–8 months of diabetes. In conclusion, STZ-induced diabetes caused changes in the erectile system that were initially reversible by a short insulin treatment, but which with time (more than 6 months) became irreversible. NO synthase activity in cavernosal tissue was normal, but the response to NG-nitro-L-arginine methyl ester was inhibited in long-term diabetes (9 months).

Neurogenically derived nitrosyl factors mediate sympathetic vasodilation in the hindlimb of the rat

1997 ◽  
Vol 272 (5) ◽  
pp. H2369-H2376 ◽  
Author(s):  
R. L. Davisson ◽  
O. S. Possas ◽  
S. P. Murphy ◽  
S. J. Lewis
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Sympathetic Neurons ◽  
Specific Inhibitor ◽  
No Synthase ◽  
Systemic Administration ◽  
Sympathetic Chain ◽  
Low Intensity ◽  
Stimulation Of

Skeletal muscle vasculature of the hindlimb is innervated by a sympathetic noncholinergic vasodilator system. The aim of this study was to determine whether this vasodilator system may represent postganglionic lumbar sympathetic neurons that synthesize and release nitric oxide (NO) or related NO-containing factors. We examined whether NO synthase (NOS)-positive postganglionic lumbar nerves innervate the hindlimb vasculature of the rat and whether the hindlimb vasodilation produced by electrical stimulation of the lumbar sympathetic chain of anesthetized rats is reduced after the systemic administration of the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI). Subpopulations of lumbar sympathetic cell bodies stained intensely for NOS. Postganglionic fibers and varicosities within the iliac and femoral arteries also stained for NOS. Double ligation of the lumbar chain demonstrated that NOS was transported from the cell bodies toward the peripheral terminals. Low-intensity electrical stimulation of the lumbar chain produced a pronounced hindlimb vasodilation that was markedly diminished by pretreatment with 7-NI (45 mg/kg i.v.). In contrast, the vasodilator potency of acetylcholine and S-nitrosocysteine were augmented by 7-NI. These results suggest that postganglionic lumbar sympathetic neurons may synthesize and release NO-containing factors.

Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

2008 ◽  
Vol 294 (1) ◽  
pp. C295-C305 ◽  
Author(s):  
James White ◽  
Theresa Guerin ◽  
Hollie Swanson ◽  
Steven Post ◽  
Haining Zhu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Myristic Acid ◽  
Acetylcholine Receptors ◽  
Diabetic Mouse ◽  
No Synthase ◽  
Diabetic Patients ◽  
No Production ◽  
Dependent Manner ◽  
Endothelial No Synthase ◽  
Stimulation Of

In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients.

Stimulation of nitric oxide from muscle cells by VIP: prejunctional enhancement of VIP release

1992 ◽  
Vol 262 (4) ◽  
pp. G774-G778 ◽  
Author(s):  
J. R. Grider ◽  
K. S. Murthy ◽  
J. G. Jin ◽  
G. M. Makhlouf
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Muscle Cells ◽  
No Synthase ◽  
No Production ◽  
Field Stimulation ◽  
Relaxant Effect ◽  
Gastric Muscle ◽  
Synthase Inhibitor ◽  
Stimulation Of

The source of nitric oxide (NO) and its role in neurally induced relaxation was examined in smooth muscle of the stomach and tenia coli. Field stimulation of gastric muscle strips was accompanied by frequency-dependent relaxation, vasoactive intestinal peptide (VIP) release, and NO production: the NO synthase inhibitor, NG-nitro-L-arginine (L-NNA) completely inhibited NO production and partly inhibited VIP release (52-54%) and relaxation (58-88%); inhibition of all three functions was reversed by L-arginine but not by D-arginine. In isolated gastric muscle cells, VIP caused relaxation and stimulated NO production: L-NNA completely inhibited NO production and partly inhibited relaxation; the inhibition was reversed by L-arginine but not by D-arginine. Abolition of NO production with only partial inhibition of relaxation implied that NO production from muscle cells induced by the action of VIP was partly responsible for relaxation. By contrast, field stimulation of tenia coli was accompanied by relaxation and VIP release but not by NO production. Neither VIP release nor relaxation was affected by L-NNA. In isolated muscle cells of tenia coli, VIP caused relaxation but did not stimulate NO production; relaxation in these cells was not affected by L-NNA. We conclude that 1) VIP is the primary relaxant transmitter in both gastric muscle and tenia coli, 2) the release of VIP in gastric muscle but not in tenia coli stimulates NO production from target muscle cells, and 3) NO amplifies the relaxant effect of VIP in muscle cells and acts presynaptically to enhance the release of VIP.

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