NO-containing factors mediate hindlimb vasodilation produced by superior laryngeal nerve stimulation

1997 ◽  
Vol 273 (1) ◽  
pp. H234-H243 ◽  
Author(s):  
O. S. Possas ◽  
S. J. Lewis
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Electrical Stimulation ◽  
Specific Inhibitor ◽  
Superior Laryngeal Nerve ◽  
Sympathetic Nerves ◽  
No Synthase ◽  
Laryngeal Nerve ◽  
Lower Intensity ◽  
Arterial Blood

The electrical stimulation (ES) of the superior laryngeal nerve (SLN) produces reflex vasodilation in the rat hindlimb. This study determined whether this vasodilation is mediated by the release of nitric oxide (NO)-containing factors (NOF) from NO synthase (NOS)-positive postganglionic lumbar sympathetic fibers that innervate the rat hindlimb vasculature. ES of the SLN (1-10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and hindlimb and mesenteric (MR) vascular resistances. The hindlimb vasodilation was not observed in rats in which the lumbar sympathetic trunk was transected 7-10 days previously. The falls in hindquarter vascular resistance (HQR) produced by lower intensity ES of the SLN were virtually abolished by the specific inhibitor of neuronal NOS 7-nitroindazole (7-NI, 45 mg/kg i.v.). The fall in HQR produced by 10 Hz ES of the SLN was not affected by 7-NI. The falls in MR produced by 1-10 Hz ES of the SLN were unaffected by 7-NI. Four consecutive episodes of ES at 10 Hz produced pronounced and equivalent reductions in MAP, HQR, and MR. After administration of 7-NI, the first ES produced similar hemodynamic responses to those observed before injection. However, each subsequent ES produced progressively and markedly smaller falls in HQR, whereas each episode of ES produced similar falls in MR. These results suggest that the reflex vasodilation in the rat hindlimb produced by ES of the SLN involves the release of newly synthesized and performed stores of NOF from NOS-positive postganglionic lumbar sympathetic nerves.

Role of nitrosyl factors in the hindlimb vasodilation elicited by baroreceptor afferent nerve stimulation

2006 ◽  
Vol 290 (3) ◽  
pp. R741-R748 ◽  
Author(s):  
Olga S. Possas ◽  
Alan Kim Johnson ◽  
Stephen J. Lewis
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Resistance ◽  
Specific Inhibitor ◽  
No Synthase ◽  
Nerve Terminals ◽  
Aortic Depressor Nerve ◽  
Arterial Blood ◽  
Afferent Fibers

This study determined whether electrical stimulation (ES) of the baroreceptor afferent fibers in the aortic depressor nerve (ADN) produces hindlimb vasodilation in pentobarbital-anesthetized rats via the release of nitric oxide (NO)-containing (nitrosyl) factors from NO synthase-positive lumbar sympathetic nerve terminals. ES of the ADN (1–10 Hz for 15 s) produced frequency-dependent reductions in mean arterial blood pressure (MAP) and mesenteric and hindlimb vascular resistance (MR and HLR, respectively). The falls in resistance were substantially smaller in hindlimb beds in which the ipsilateral lumbar sympathetic chain had been transected 7–10 days previously. The maximal falls in MR and hindquarter vascular resistance (HQR) produced by 1- to 10-Hz ES of the ADN were unaffected by the specific inhibitor of neuronal NO synthase 7-nitroindazole (7-NI, 45 mg/kg iv). However, the total falls in HQR (mmHg·kHz−1·s) produced by these stimuli were significantly diminished by 7-NI, whereas the total falls in MR were not affected. Four successive episodes of 10-Hz ES produced equivalent reductions in MAP, MR, and HQR. The peak changes in these parameters were not affected by 7-NI. However, the total falls in HQR progressively diminished with each successive stimulus, whereas the total falls in MR remained unchanged. These results provide evidence that the hindlimb vasodilation produced by ES of baroreceptor afferents within the ADN may involve the activation of postganglionic lumbar sympathetic vasodilator fibers, which release newly synthesized and preformed nitrosyl factors.

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.

Nitric oxide modulates elicitation of reflex swallowing from the pharynx in rats

2006 ◽  
Vol 291 (3) ◽  
pp. R651-R656 ◽  
Author(s):  
Hiroshi Kijima ◽  
Tomio Shingai ◽  
Yoshihiro Takahashi ◽  
Yuka Kajii ◽  
Shin-ichi Fukushima ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
Intraperitoneal Administration ◽  
Superior Laryngeal Nerve ◽  
Laryngeal Nerve ◽  
Electromyographic Activity ◽  
No Donor ◽  
Pharyngeal Branch ◽  
Prolonged Latency ◽  
Stimulation Of

The pharynx is very important for elicitation of reflex swallowing. The region of the pharynx is innervated by the pharyngeal branch of the glossopharyngeal nerve (GPN-ph). Nitric oxide (NO) plays an important role in various physiological functions. The purpose of this study is to investigate the contribution of NO to reflex swallowing evoked by electrical stimulation of the GPN-ph. Swallowing was evoked in urethane-anesthetized rats by application of repetitive electrical stimulation (10- to 20-μA amplitude, 10- to 20-Hz frequency, 1.0-ms duration) to the central cut end of the GPN-ph or superior laryngeal nerve. Swallowing was identified by electromyographic activity of the mylohyoid muscle. Latency to the first swallow and the interval between swallows were measured. Intravenous administration of NG-nitro-l-arginine (l-NNA, 0.6 mg/kg), a nonselective inhibitor of NO synthase (NOS), extremely prolonged latency to the first swallow and the interval between swallows evoked by the GPN-ph. Intraperitoneal administration of 7-nitroindazole (5.0 mg/kg), a selective inhibitor of neuronal NOS, significantly prolonged latency to the first swallow and the interval between swallows evoked by the GPN-ph. Administration of l-arginine (an NO donor, 500 mg/kg) and sodium nitroprusside (an NO releaser, 0.6 mg/kg) restored the suppression of swallowing induced by the NOS inhibitor. Superior laryngeal nerve-evoked swallowing was suppressed by administration of a higher dose of l-NNA (6.0 mg/kg). Swallowing evoked by water stimulation of the pharynx was also suppressed by l-NNA (0.6 mg/kg). These results suggest that NO plays an important role in signal processing for initiation of reflex swallowing from the pharynx.

Abstract 2046: Hypercapnic Resuscitation Improves Survival and Neurological Outcomes by Nitric Oxide Synthase-Mediated Enhancement of Brain Perfusion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Wei-Tien Chang ◽  
Lay-San Gan ◽  
Chiang-Ting Chien ◽  
Chien-Hua Huang ◽  
Huei-Wen Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Arrest ◽  
Apoptotic Cell ◽  
Brain Perfusion ◽  
No Synthase ◽  
Neurological Injury ◽  
Neurological Outcomes ◽  
Arterial Blood ◽  
The Brain

Neurological injury is one of the major causes of morbidity and mortality following cardiac arrest and cardiopulmonary resuscitation (CPR). Brain perfusion is usually compromised in the post-resuscitation phase, which inevitably lengthens the ischemic insult of the brain. Hypercapnia has been reported to cause cerebral vasodilatation. We therefore sought to study the potentials of hypercapnic resuscitation in improving the brain perfusion as well as survival and neurological prognoses. Using an established rat model of asphyxial cardiac arrest (6 min) and CPR, we employed hypercapnic (5% CO 2 , 95% O 2 ) ventilation during CPR and the first 2 h post-resuscitation, and compared the brain perfusion with normocapnia (5% N 2 , 95% O 2 ) control. The blood pressure was continuously monitored, with arterial blood sampled regularly for gas analysis. The tissue perfusion of the brain was measured by OxyLyte 2000E perfusion sensor. In a subgroup the survival and neurological outcomes were monitored up to 3 days. TdT-mediated dUTP nick-ends labeling (TUNEL) stain and Bax/Bcl2 of the brain were assessed as indicators of apoptotic cell death. The PaCO 2 was significantly higher ( P <0.001) and pH significantly lower ( P <0.001) in hypercapnia group during the first 2 h post-resuscitation. No difference was noted in PaO 2 or blood pressure. In normocapnia control, the brain perfusion was significantly reduced in the first 30 min post-resuscitation. Hypercapnic ventilation enhanced brain perfusion during this period ( P <0.05). The survival and neurological outcomes were also improved (LogRank P <0.05), which was consistent with the decrease in TUNEL stain and Bax/Bcl2. If nitric oxide (NO) synthase inhibitor N ω -nitro-L-arginine methyl ester (L-NAME, 10 mg/kg) was cotreated with hypercapnia, the increased brain perfusion and reduced TUNEL and Bax/Bcl2 were reversed. The improved survival and neurological outcomes were also abrogated. Hypercapnic ventilation during CPR and early post-resuscitation phase improves brain perfusion and hence survival and neurological outcomes. This is in part mediated by NO synthase-related vasodilatation.

scholarly journals Increased nitric oxide activity in a rat model of acute pancreatitis

Gut ◽  
1998 ◽  
Vol 43 (4) ◽  
pp. 564-570 ◽  
Author(s):  
R A Al-Mufti ◽  
R C N Williamson ◽  
R T Mathie
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Acute Pancreatitis ◽  
Arterial Blood Pressure ◽  
Tissue Damage ◽  
No Synthase ◽  
Arterial Blood ◽  
Inducible No Synthase ◽  
Cellular Localisation ◽  
Male Wistar Rats

Background—Overproduction of nitric oxide (NO) via induction of the inducible NO synthase (iNOS) is an important factor in the haemodynamic disturbances of several inflammatory states.Aims—To identify the role of NO in a caerulein induced model of acute pancreatitis in the rat.Methods—Arterial blood pressure and plasma NO metabolites were measured at zero and seven hours in adult male Wistar rats administered caerulein (n=10) or saline (n=10). Pancreatic activity of NOS (inducible and constitutive) was assayed biochemically. The pancreatic expression and cellular localisation of NOS and nitrotyrosine (a marker of peroxynitrite induced oxidative tissue damage) were characterised immunohistochemically.Results—Compared with controls at seven hours, the pancreatitis group displayed raised plasma NO metabolites (mean (SEM) 70.2 (5.9) versus 22.7 (2.2) μmol/l, p<0.0001) and reduced mean arterial blood pressure (88.7 (4.6) versus 112.8 (4.1) mm Hg, p=0.008). There was notable iNOS activity in the pancreatitis group (3.1 (0.34) versus 0.1 (0.01) pmol/mg protein/min, p<0.0001) with reduced constitutive NOS activity (0.62 (0.12) versus 0.96 (0.08) pmol/mg protein/min, p=0.031). The increased expression of iNOS was mainly localised within vascular smooth muscle cells (p=0.003 versus controls), with positive perivascular staining for nitrotyrosine (p=0.0012 versus controls).Conclusions—In this experimental model of acute pancreatitis, iNOS induction and oxidative tissue damage in the pancreas is associated with raised systemic NO and arterial hypotension. Excess production of NO arising from the inducible NO synthase may be an important factor in the systemic and local haemodynamic disturbances associated with acute pancreatitis.

Renal effects of nitric oxide synthase inhibition in conscious water-loaded dogs

2001 ◽  
Vol 281 (2) ◽  
pp. R584-R590 ◽  
Author(s):  
Thomas V. Peterson ◽  
Claus Emmeluth ◽  
Peter Bie
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Sodium Excretion ◽  
Volume Expansion ◽  
Excretion Rate ◽  
No Synthase ◽  
Urine Flow ◽  
Water Diuresis ◽  
Renal Effects ◽  
Arterial Blood

The renal effects of the nitric oxide (NO) synthase inhibitor nitro-l-arginine methyl ester (l-NAME) were investigated in conscious dogs undergoing sustained water diuresis and replacement of urinary sodium losses. Experiments were performed with and without additional extracellular volume expansion (isotonic saline, 2% body wt). l-NAME (10 μg · kg−1 · min−1) infused during water diuresis decreased urine flow (2.5 ± 0.2 to 1.5 ± 0.3 ml/min), free water clearance (1.9 ± 0.2 to 1.0 ± 0.2 ml/min), and sodium excretion (4.0 ± 1.7 to 2.1 ± 0.6 μmol/min). Arterial blood pressure increased from 112 ± 2 to 126 ± 3 mmHg, but creatinine clearance did not measurably change. Plasma endothelin and vasopressin concentrations and plasma renin activity (PRA) were unchanged. Urinary endothelin concentration increased (3.4 ± 0.8 to 6.2 ± 1.7 pg/ml), but the excretion rate remained constant. l-Arginine infusion (0.6 mg · kg−1 · min−1) along withl-NAME abolished the renal effects but not the blood pressure increase. Volume expansion increased urine flow (2.5 ± 0.4 to 5.7 ± 0.5 ml/min) and sodium excretion (3.8 ± 1.6 to 76.5 ± 14.5 μmol/min). l-NAME attenuated the renal effects of volume expansion: urine flow increased to 2.8 ± 0.7 ml/min and sodium excretion to 34 ± 17 μmol/min. PRA decreased with control volume expansion but not during l-NAME. Urinary endothelin levels were elevated by l-NAME, decreased with volume expansion in all series, but excretion rate remained constant. Infusion of l-arginine partially reversed these effects of l-NAME. The results demonstrate that NO synthase inhibition increases blood pressure and blunts the renal responses to water and saline loading.

Effects of Neuroactive Amino Acids Derivatives on Cardiac and Cerebral Mitochondria and Endothelial functions in Animals Exposed to Stress

2017 ◽  
Vol 2 (2) ◽  
pp. 34
Author(s):  
TA Popova ◽  
II Prokofiev ◽  
IS Mokrousov ◽  
Valentina Perfilova ◽  
AV Borisov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Platelet Aggregation ◽  
Atp Synthesis ◽  
Elevated Concentration ◽  
Blood Pressure Monitor ◽  
Pressure Monitor ◽  
Griess Reagent ◽  
Arterial Blood ◽  
Endothelial Functions

Introduction: To study the effects of glufimet, a new derivative of glutamic acid, and phenibut, a derivative of γ-aminobutyric acid (GABA), on cardiac and cerebral mitochondria and endothelial functions in animals following exposure to stress and inducible nitric oxide synthase (iNOS) inhibition. Methods: Rats suspended by their dorsal cervical skin fold for 24 hours served as the immobilization and pain stress model. Arterial blood pressure was determined using a non-invasive blood pressure monitor. Mitochondrial fraction of heart and brain homogenates were isolated by differential centrifugation and analysed for mitochondrial respiration intensity, lipid peroxidation (LPO) and antioxidant enzyme activity using polarographic method. The concentrations of nitric oxide (NO) terminal metabolites were measured using Griess reagent. Hemostasis indices were evaluated. Platelet aggregation was estimated using modified version of the Born method described by Gabbasov et al., 1989. Results: The present study demonstrated that stress leads to an elevated concentration of NO terminal metabolites and LPO products, decreased activity of antioxidant enzymes, reduced mitochondrial respiratory function, and endothelial dysfunction. Inhibition of iNOS by aminoguanidine had a protective effect. Phenibut and glufimet inhibited a rise in stress-induced nitric oxide production. This resulted in enhanced coupling of substrate peroxidation and ATP synthesis. The reduced LPO processes caused by glufimet and phenibut normalized the endothelial function which was proved by the absence of average daily blood pressure (BP) elevation episodes and a significant increase in platelet aggregation level. Conclusion: Glufimet and phenibut restrict the harmful effects of stress on the heart and brain possibly by modulating iNOS activity.

Systemic and regional hemodynamics after nitric oxide synthase inhibition: role of a neurogenic mechanism

1994 ◽  
Vol 267 (1) ◽  
pp. R84-R88 ◽  
Author(s):  
M. Huang ◽  
M. L. Leblanc ◽  
R. L. Hester
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Cardiac Output ◽  
No Synthase ◽  
Before And After ◽  
Regional Hemodynamics ◽  
Autonomic Blockade ◽  
Infusion Of Norepinephrine ◽  
Oxide Synthase

The study tested the hypothesis that the increase in blood pressure and decrease in cardiac output after nitric oxide (NO) synthase inhibition with N omega-nitro-L-arginine methyl ester (L-NAME) was partially mediated by a neurogenic mechanism. Rats were anesthetized with Inactin (thiobutabarbital), and a control blood pressure was measured for 30 min. Cardiac output and tissue flows were measured with radioactive microspheres. All measurements of pressure and flows were made before and after NO synthase inhibition (20 mg/kg L-NAME) in a group of control animals and in a second group of animals in which the autonomic nervous system was blocked by 20 mg/kg hexamethonium. In this group of animals, an intravenous infusion of norepinephrine (20-140 ng/min) was used to maintain normal blood pressure. L-NAME treatment resulted in a significant increase in mean arterial pressure in both groups. L-NAME treatment decreased cardiac output approximately 50% in both the intact and autonomic blocked animals (P < 0.05). Autonomic blockade alone had no effect on tissue flows. L-NAME treatment caused a significant decrease in renal, hepatic artery, stomach, intestinal, and testicular blood flow in both groups. These results demonstrate that the increase in blood pressure and decreases in cardiac output and tissue flows after L-NAME treatment are not dependent on a neurogenic mechanism.

scholarly journals Beneficial haemodynamic effect of indomethacin during endotoxin shock in anaesthetized pigsputative involvement of nitric oxide?

1995 ◽  
Vol 4 (2) ◽  
pp. 117-123 ◽  
Author(s):  
T. Mózes ◽  
E. M. van Gelderen ◽  
E. J. Mylecharane ◽  
P. R. Saxena
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Beneficial Effect ◽  
Endotoxic Shock ◽  
Haemodynamic Effect ◽  
Experimental Period ◽  
Endotoxin Shock ◽  
Arterial Blood ◽  
Imminent Death ◽  
Beneficial Haemodynamic Effect

Endotoxin shock was induced in 31 anaesthetized pigs by infusion of 5 μg/kg of Escbeicbia coli endotoxin (LPS) over 60 min into the superior mesenteric artery. Fifteen of these pigs died within 30 min of the start of LPS infusion whereas the remaining 16 survived the experimental period of 2 h. In a group of nine pigs indomethacin (2 mg/kg, i.v.)was inected 20–25 rain after the start of LPS infusion at which time mean arterial blood pressure (MABP) had decreased below 40 mmHg indicating imminent death. Indomethacin immediately reversed the hypotension. In another group of five pigs, NG-nitro L-arginine-methyl ester (L-NAME, 1 and 3 mg/kg)was iniected 10 and 5 min, respectively, before the expected death without any beneficial effect on the hypotension. Three rain after the last dose of L-NAME, indomethacin (2 mg/kg, i.v.) was iniected. In three animals the hypotension was reserved by indomethacin, although this beneficial effect was delayed in comparison with the LP-Streated group not receiving L-NAME. Four pigs were pretreated with L-NAME, 3 mg/kg, i.v., 10 min prior to LPS infusion. All pretreated animals tended to die within 30 min of the start of the LPS infusion. Five rain before the expected death (20–25 rain after the start of LPS infusion) indomethacin (2 mg/kg) was inected. In three of these animals indomethacin reversed hypotenston and prevented death. Interestingly, this rise in the MABP developed very slowly. These results suggest that the beneficial effect of indomethacin in endotoxin shock might be related partially to interference with nitric oxide, which is not the only factor determining blood pressure levels during endotoxic shock.

Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat

2007 ◽  
Vol 293 (4) ◽  
pp. R1657-R1665 ◽  
Author(s):  
Annie Beauséjour ◽  
Véronique Houde ◽  
Karine Bibeau ◽  
Rébecca Gaudet ◽  
Jean St-Louis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitrosative Stress ◽  
Gestational Hypertension ◽  
Sodium Intake ◽  
Pregnant Rats ◽  
High Sodium ◽  
High Sodium Intake ◽  
Arterial Blood ◽  
Cardiac Ventricle

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F2α (8-iso-PGF2α) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na+-K+-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-α)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na+-K+-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF2α, and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.

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