Differential sympathetic nerve responses to nitric oxide synthase inhibition in anesthetized rats

1995 ◽  
Vol 269 (4) ◽  
pp. R807-R813 ◽  
Author(s):  
T. Hirai ◽  
T. I. Musch ◽  
D. A. Morgan ◽  
K. C. Kregel ◽  
D. E. Claassen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sympathetic Nerve ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Important Means ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Tonic Excitation

Recent studies have suggested that the interaction between the sympathetic nervous system and nitric oxide (NO) or nitrosyl factors may be an important means by which arterial blood pressure is regulated. We investigated whether NO synthase (NOS) inhibition modulates basal sympathetic nerve discharge (SND) in baroreceptor-innervated and -denervated, chloralose-anesthetized Sprague-Dawley rats. We recorded mean arterial pressure (MAP), renal SND, and lumbar SND before and after administration of the NOS inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg iv). Two minutes after L-NAME administration in baroreceptor-innervated rats, MAP increased (+23 +/- 3 mmHg), whereas renal (-45 +/- 6%, n = 7) and lumbar (-35 +/- 2%, n = 6) SND significantly decreased from control levels. These changes persisted for up to 20 min after L-NAME administration. In baroreceptor-denervated rats, L-NAME increased MAP (+40 +/- 6 mmHg) and decreased lumbar SND (n = 7) (-37 +/- 10% from control at 20 min post-L-NAME). In contrast, renal SND progressively increased (+33 +/- 8% at 20 min post-L-NAME) from control after L-NAME administration in baroreceptor-denervated rats (n = 7). These results demonstrate that NOS inhibition can produce nonuniform changes in SND in baroreceptor-denervated rats and suggest that endogenous nitrosyl factors provide tonic excitation to lumbar SND, whereas they provide a tonic restraint to renal SND.

Nitric oxide modulation of glutamatergic, baroreflex, and cardiopulmonary transmission in the nucleus of the solitary tract

2005 ◽  
Vol 288 (1) ◽  
pp. H256-H262 ◽  
Author(s):  
Ana Carolina Rodrigues Dias ◽  
Melissa Vitela ◽  
Eduardo Colombari ◽  
Steven W. Mifflin
Keyword(s):  
Nitric Oxide ◽  
Solitary Tract ◽  
Glutamatergic Transmission ◽  
Sprague Dawley ◽  
Renal Sympathetic Nerve Activity ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Nos Inhibitor ◽  
The Right ◽  
Oxide Synthase

The neuromodulatory effect of NO on glutamatergic transmission has been studied in several brain areas. Our previous single-cell studies suggested that NO facilitates glutamatergic transmission in the nucleus of the solitary tract (NTS). In this study, we examined the effect of the nitric oxide synthase (NOS) inhibitor NG-nitro-l-arginine methyl ester (l-NAME) on glutamatergic and reflex transmission in the NTS. We measured mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) from Inactin-anesthetized Sprague-Dawley rats. Bilateral microinjections of l-NAME (10 nmol/100 nl) into the NTS did not cause significant changes in basal MAP, HR, or RSNA. Unilateral microinjection of ( RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA, 1 pmol/100 nl) into the NTS decreased MAP and RSNA. Fifteen minutes after l-NAME microinjections, AMPA-evoked cardiovascular changes were significantly reduced. N-methyl-d-aspartate (NMDA, 0.5 pmol/100 nl) microinjection into the NTS decreased MAP, HR, and RSNA. NMDA-evoked falls in MAP, HR, and RSNA were significantly reduced 30 min after l-NAME. To examine baroreceptor and cardiopulmonary reflex function, l-NAME was microinjected at multiple sites within the rostro-caudal extent of the NTS. Baroreflex function was tested with phenylephrine (PE, 25 μg iv) before and after l-NAME. Five minutes after l-NAME the decrease in RSNA caused by PE was significantly reduced. To examine cardiopulmonary reflex function, phenylbiguanide (PBG, 8 μg/kg) was injected into the right atrium. PBG-evoked hypotension, bradycardia, and RSNA reduction were significantly attenuated 5 min after l-NAME. Our results indicate that inhibition of NOS within the NTS attenuates baro- and cardiopulmonary reflexes, suggesting that NO plays a physiologically significant neuromodulatory role in cardiovascular regulation.

scholarly journals The NOS Inhibitor, 7-Nitroindazole, Decreases Focal Infarct Volume but Not the Response to Topical Acetylcholine in Pial Vessels

1994 ◽  
Vol 14 (6) ◽  
pp. 924-929 ◽  
Author(s):  
Tazuka Yoshida ◽  
Volker Limmroth ◽  
Katsumi Irikura ◽  
Michael A. Moskowitz
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Infarct Volume ◽  
Ischemic Injury ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Mca Occlusion ◽  
Permanent Occlusion ◽  
Nos Inhibitor ◽  
Oxide Synthase

We examined whether 7-nitroindazole (7-NI), a putative inhibitor of neuronal nitric oxide synthase (nNOS), decreases cerebral infarction 24 h after proximal middle cerebral artery (MCA) occlusion. In preliminary experiments, we determined that 7-NI (25, 50, and 100 mg/kg i.p.) decreased nitric oxide synthase (NOS) activity within cerebral cortex by 40–60% when measured up to 120 min, but not 240 min after administration. At 25 or 50 mg/kg, 7-NI did not alter the systemic arterial blood pressure or the dilation of pial arterioles after topical acetylcholine (10 and 100 μ M). To examine the effect of 7-NI on infarct size, 55 Sprague–Dawley halothaneanesthetized rats were subjected to proximal MCA occlusion (modified Tamura method). Five minutes after occlusion, 7-NI (25 or 50 mg/kg i.p.) or vehicle was injected. Animals treated with 25 or 50 mg/kg showed 25 and 27% reductions in infarct volume, respectively. Coadministration of l-arginine (300 mg/kg i.p.) plus 7-NI (25 mg/kg i.p.) reversed the effect. If, indeed, the effects of 7-NI are mediated by inhibition of nNOS activity, these results suggest that enzymatic products of the neuronal isoform promote ischemic injury and that they do so at least within the first few hours after permanent occlusion. The results also emphasize the importance of developing strategies to selectively inhibit the neuronal isoform inasmuch as we observed previously that administering the less selective NOS inhibitor, Nω-nitro-l-arginine (L-NA), in the same model either caused no change or increased the volume of ischemic injury.

Inhibition of Nitric Oxide Synthase Prevents Hyporesponsiveness to Inhaled Nitric Oxide in Lungs from Endotoxin-challenged Rats 

1999 ◽  
Vol 91 (1) ◽  
pp. 215-221 ◽  
Author(s):  
Alexandra Holzmann ◽  
Claire Manktelow ◽  
Friedemann J. H. Taut ◽  
Kenneth D. Bloch ◽  
Warren Zapol
Keyword(s):  
Nitric Oxide ◽  
No Production ◽  
Sprague Dawley ◽  
Pulmonary Vasodilator ◽  
Sprague Dawley Rats ◽  
Vascular Responsiveness ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Inhaled No ◽  
Lps Treatment

Background Inhalation of nitric oxide (NO) selectively dilates the pulmonary circulation and improves arterial oxygenation in patients with adult respiratory distress syndrome (ARDS). In approximately 60% of patients with septic ARDS, minimal or no response to inhaled NO is observed. Because sepsis is associated with increased NO production by inducible NO synthase (NOS2), the authors investigated whether NOS inhibition alters NO responsiveness in rats exposed to gram-negative lipopolysaccharide (LPS). Methods Sprague-Dawley rats were treated with 0.4 mg/kg Escherichia coli O111:B4 LPS with or without dexamethasone (inhibits NOS2 gene expression; 5 mg/kg), L-NAME (a nonselective NOS inhibitor; 7 mg/kg), or aminoguanidine (selective NOS2 inhibitor; 30 mg/kg). Sixteen hours after LPS treatment, lungs were isolated-perfused; a thromboxane-analog U46619 was added to increase pulmonary artery pressure (PAP) by 5 mmHg, and the pulmonary vasodilator response to inhaled NO was measured. Results Ventilation with 0.4, 4, and 40 ppm NO decreased the PAP less than in lungs of LPS-treated rats (0.75+/-0.25, 1.25+/-0.25, 1.75+/-0.25 mmHg) than in lungs of control rats (3+/-0.5, 4.25+/-0.25, 4.5+/-0.25 mmHg; P < 0.01). Dexamethasone treatment preserved pulmonary vascular responsiveness to NO in LPS-treated rats (3.75+/-0.25, 4.5+/-0.25, 4.5+/-0.5 mmHg, respectively; P < 0.01 vs. LPS, alone). Responsiveness to NO in LPS-challenged rats was also preserved by treatment with L-NAME (3.0+/-1.0, 4.0+/-1.0, 4.0+/-0.75 mmHg, respectively; P < 0.05 vs. LPS, alone) or aminoguanidine (1.75+/-0.25, 2.25+/-0.5, 2.75+/-0.5 mmHg, respectively; P < 0.05 vs. LPS, alone). In control rats, treatment with dexamethasone, L-NAME, and aminoguanidine had no effect on inhaled NO responsiveness. Conclusion These observations demonstrate that LPS-mediated increases in pulmonary NOS2 are involved in decreasing responsiveness to inhaled NO.

Functional NOS 1 in the rat mesenteric arterial bed

2002 ◽  
Vol 283 (2) ◽  
pp. H658-H663 ◽  
Author(s):  
Jennifer C. Sullivan ◽  
Ararat D. Giulumian ◽  
David M. Pollock ◽  
Leslie C. Fuchs ◽  
Jennifer S. Pollock
Keyword(s):  
Nitric Oxide ◽  
Molecular Mass ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Sprague Dawley Rats ◽  
Lower Molecular Mass ◽  
Mesenteric Arterial Bed ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Mass Form

Previously we have demonstrated functional nitric oxide synthase (NOS) 1 in large arteries. Because resistance arteries largely determine blood pressure, this study examined whether functional NOS 1 also exists in resistance arteries. Phenylephrine (PE) contraction was measured in the absence and presence of the NOS 1 inhibitor N 5-(1-imino-3-butenyl)-l-ornithine (VNIO) in isolated mesenteric resistance arteries (endothelium intact and denuded) from Sprague-Dawley rats. For NOS 1 activity and expression, the mesenteric arterial bed was separated into cytosolic and particulate fractions. NOS activity was assayed by measuring the conversion of [3H]arginine to [3H]citrulline inhibited by a nonselective NOS inhibitor or VNIO. VNIO increased PE sensitivity in endothelium-intact and -denuded arteries. In cytosolic and particulate fractions of the arterial bed, ∼40% of NOS activity was inhibited by VNIO. Immunoprecipitation and Western blot analysis revealed two NOS 1 immunoreactive bands. One band corresponded to the rat brain isoform, whereas the second was of a slightly lower molecular mass. The cytosolic fraction contained both isoforms; however, the particulate fraction had only the lower molecular mass form. These studies demonstrate the existence of functional NOS 1 in resistance arteries.

Loss of hypoxic pulmonary vasoconstriction in chronic pneumonia is not mediated by nitric oxide

1993 ◽  
Vol 265 (5) ◽  
pp. H1523-H1528 ◽  
Author(s):  
D. G. McCormack ◽  
N. A. Paterson
Keyword(s):  
Nitric Oxide ◽  
Pressor Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Sprague Dawley ◽  
Absolute Increase ◽  
Pulmonary Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Before And After ◽  
Inflammatory Processes ◽  
The Difference

In pulmonary inflammatory processes such as pneumonia there is diminished hypoxic pulmonary vasoconstriction (HPV). We investigated whether the attenuated HPV in pneumonia is a due to excess nitric oxide (NO) release. Sprague-Dawley rats were anesthetized, and a slurry (0.06 ml) of infected agar beads (containing 6 x 10(5) Pseudomonas aeruginosa organisms) or control (sterile) beads was then injected into a distal bronchus through a tracheotomy. After the establishment of a chronic P. aeruginosa pneumonia (7-10 days later) animals were instrumented for hemodynamic monitoring, and the response to exposure to hypoxic gas (fraction of inspired O2 = 0.08) was recorded before and after the administration of NG-monomethyl-L-arginine (L-NMMA; 50 mg/kg), an inhibitor of NO synthesis. The hypoxic pressor response, as assessed by the absolute increase in pulmonary arterial pressure (PAP) and total pulmonary resistance (TPR), was reduced in infected animals compared with control animals. The change in PAP and TPR was 8.5 +/- 0.7 and 0.053 +/- 0.007, respectively, in control animals compared with 5.9 +/- 0.5 and 0.041 +/- 0.011 in infected animals. After L-NMMA the increase in PAP and TPR during hypoxia was greater in both control and infected animals. However, treatment with L-NMMA did not affect the difference between control and infected animals. We conclude that excess release of NO does not account for the attenuated hypoxic pressor response in pneumonia.

scholarly journals Hypertensive female Sprague-Dawley rats require an intact nitric oxide synthase system for compensatory increases in renal regulatory T cells

2020 ◽  
Vol 319 (2) ◽  
pp. F192-F201
Author(s):  
Lindsey A. Ramirez ◽  
Ellen E. Gillis ◽  
Jacqueline B. Musall ◽  
Riyaz Mohamed ◽  
Elizabeth Snyder ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
T Cells ◽  
Angiotensin Ii ◽  
Nitric Oxide Synthase ◽  
Regulatory T Cells ◽  
Female Rats ◽  
Sprague Dawley ◽  
Albumin Excretion ◽  
Sprague Dawley Rats ◽  
Oxide Synthase

We have previously shown that hypertensive female rats have more regulatory T cells (Tregs), which contribute more to blood pressure (BP) control in female versus male rats. Based on known protective properties of Tregs, the goal of the present study was to investigate the mechanisms by which female rats maintain Tregs. The present study was designed to 1) compare the impact of three hypertension models on the percentage of renal Tregs and 2) test the hypothesis that nitric oxide synthase (NOS) inhibition prevents increases in renal Tregs and exacerbates renal damage in female Sprague-Dawley rats. Rats (11–14 wk old) were randomized to one of the following four groups: control, norepinephrine (NE) infusion, angiotensin II infusion, or the NOS inhibitor Nω-nitro-l-arginine methyl ester (l-NAME) in drinking water. BP was measured via tail cuff. After 2 wk of treatment, kidneys were isolated and processed to measure Tregs via flow cytometric analysis and renal injury via urinary albumin excretion, plasma creatinine, and histological analyses. Hypertensive treatments increased BP in all experimental animals. Increases in BP in norepinephrine-and angiotensin II-treated rats were associated with increases in renal Tregs versus control. In contrast, l-NAME treatment decreased Tregs compared with all groups. l-NAME treatment modestly increased albumin excretion. However, plasma creatinine was comparable among the groups, and there was no histological evidence of glomerular or tubular injury. This study provides insights into the mechanisms regulating renal Tregs and supports that an intact NOS system is crucial for female rats to have BP-related increases in renal Tregs.

scholarly journals Systemic hypotensive effects of testosterone are androgen structure-specific and neuronal nitric oxide synthase-dependent

2015 ◽  
Vol 309 (2) ◽  
pp. R189-R195 ◽  
Author(s):  
Mercedes Perusquía ◽  
Clayton D. Greenway ◽  
Lisa M. Perkins ◽  
John N. Stallone
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Sprague Dawley ◽  
Peripheral Vasculature ◽  
Similar Reduction ◽  
Arterial Blood ◽  
Sd Rats ◽  
Oxide Synthase

Testosterone (TES) and other androgens exert a direct vasorelaxing action on the vasculature in vitro that is structurally specific and independent of cytosolic androgen receptor (AR). The effects of intravenous androgen infusions on mean arterial blood pressure (BP) and heart rate (HR) were determined in conscious, unrestrained, chronically catheterized, ganglionically blocked (hexamethonium, HEX; 30 mg/kg ip) male Sprague-Dawley (SD) and testicular-feminized male (Tfm; AR-deficient) rats, 16–20 wk of age. BP and HR were recorded at baseline and with increasing doses of androgens (0.375–6.00 μmol·kg−1·min−1 iv; 10 min/dose). Data are expressed as means ± SE ( n = 5–8 rats/group). In SD rats, baseline BP and HR averaged 103 ± 4 mmHg and 353 ± 12 beats/min (bpm). TES produced a dose-dependent reduction in BP to a low of 87 ± 4 mmHg (Δ16%), while HR was unchanged (354 ± 14 bpm). Neither BP (109 ± 3 mmHg) nor HR (395 ± 13 bpm) were altered by vehicle (10% EtOH in 0.9% saline; 0.15 ml·kg−1·min−1, iv). In Tfm, TES produced a similar reduction in BP (99 ± 3 to 86 ± 3 mmHg, Δ13%); HR was unchanged (369 ± 18 bpm). In SD, 5β-dihydrotestosterone (genomically inactive metabolite) produced a greater reduction in BP than TES (102 ± 2 to 79 ± 2 mmHg, Δ23%); HR was unchanged (361 ± 9). A 20-μg iv bolus of sodium nitroprusside in both SD and Tfm rats reduced BP 30–40 mmHg, while HR was unchanged, confirming blockade by HEX. Pretreatment of SD rats with neuronal nitric oxide synthase (nNOS) inhibitor (S-methyl-thiocitrulline, SMTC; 20 μg·kg−1·min−1 × 30 min) abolished the hypotensive effects of TES infusion on BP (104 ± 2 vs. 101 ± 2 mmHg) and HR (326 ± 11 vs. 324 ± 8 bpm). These data suggest the systemic hypotensive effect of TES and other androgens involves a direct vasodilatory action on the peripheral vasculature which, like the effect observed in isolated arteries, is structurally specific and AR-independent, and involves activation of nNOS.

Relationship between muscle sympathetic nerve activity and systemic hemodynamics during nitric oxide synthase inhibition in humans

2006 ◽  
Vol 291 (3) ◽  
pp. H1378-H1383 ◽  
Author(s):  
N. Charkoudian ◽  
M. J. Joyner ◽  
S. A. Barnes ◽  
C. P. Johnson ◽  
J. H. Eisenach ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sympathetic Nerve ◽  
Total Peripheral Resistance ◽  
Sympathetic Nerve Activity ◽  
Muscle Sympathetic Nerve Activity ◽  
Peripheral Resistance ◽  
Nerve Activity ◽  
Lower Baseline ◽  
Nos Inhibitor ◽  
Oxide Synthase

Large interindividual differences exist in resting sympathetic nerve activity (SNA) among normotensive humans with similar arterial pressure (AP). We recently showed inverse relationships of resting SNA with cardiac output (CO) and vascular adrenergic responsiveness that appear to balance the influence of differences in SNA on blood pressure. In the present study, we tested whether nitric oxide (NO)-mediated vasodilation has a role in this balance by evaluating hemodynamic responses to systemic NO synthase (NOS) inhibition in individuals with low and high resting muscle SNA (MSNA). We measured MSNA via peroneal microneurography, CO via acetylene uptake and AP directly, at baseline and during increasing systemic doses of the NOS inhibitor NG-monomethyl-l-arginine (l-NMMA). Baseline MSNA ranged from 9 to 38 bursts/min (13 to 68 bursts/100 heartbeats). l-NMMA caused dose-dependent increases in AP and total peripheral resistance and reflex decreases in CO and MSNA. Increases in AP with l-NMMA were greater in individuals with high baseline MSNA ( PANOVA < 0.05). For example, after 8.5 mg/kg of l-NMMA, in the low MSNA subgroup ( n = 6, 28 ± 4 bursts/100 heartbeats), AP increased 9 ± 1 mmHg, whereas in the high-MSNA subgroup ( n = 6, 58 ± 3 bursts/100 heartbeats), AP increased 15 ± 2 mmHg ( P < 0.01). The high-MSNA subgroup had lower baseline CO and smaller decreases in CO with l-NMMA, but changes in total peripheral resistance were not different between groups. We conclude that differences in CO among individuals with varying sympathetic traffic have important hemodynamic implications during disruption of NO-mediated vasodilation.

Nitric Oxide in the Gracile Nucleus Mediates Depressor Response to Acupuncture (ST36)

2003 ◽  
Vol 90 (2) ◽  
pp. 780-785 ◽  
Author(s):  
Shuang Chen ◽  
Sheng-Xing Ma
Keyword(s):  
Nitric Oxide ◽  
Cardiovascular Response ◽  
Cardiovascular Responses ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Gracile Nucleus ◽  
Sprague Dawley Rats ◽  
Antisense Oligos ◽  
Stimulation Of

The purpose of these studies was to determine the role of gracile nucleus and the effects of l-arginine-derived nitric oxide (NO) synthesis in the nucleus on the cardiovascular responses to electroacupuncture (EA) stimulation of “Zusanli” (ST36). Arterial blood pressure and heart rate were monitored during EA stimulation of ST36 following microinjections of agents into gracile nucleus. EA ST36 produced depressor and bradycardiac responses in anesthetized Sprague-Dawley rats. The cardiovascular responses to EA ST36 were blocked by bilateral microinjection of lidocaine into gracile nucleus. Microinjection of l-arginine into gracile nucleus facilitated the hypotensive and bradycardiac responses to EA ST36. The cardiovascular responses to EA ST36 were attenuated by bilateral microinjection of neuronal NO synthase (nNOS) antisense oligos into gracile nucleus. Microinjection of nNOS sense oligos into gracile nucleus did not alter the cardiovascular response to EA ST36. The results demonstrate that a blockade of neuronal conduction in the gracile nucleus inhibits the cardiovascular responses to EA ST36. The hypotensive and bradycardiac responses to EA ST36 are modified by influences of l-arginine-derived NO synthesis in the gracile nucleus. We conclude that NO plays an important role in mediating the cardiovascular responses to EA ST36 through gracile nucleus.

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