Nitric Oxide Synthase Inhibition Depresses the Height of the Cerebral Blood Flow–Pressure Autoregulation Curve during Moderate Hypotension

2003 ◽  
Vol 23 (9) ◽  
pp. 1085-1095 ◽  
Author(s):  
Stephen C. Jones ◽  
Kirk A. Easley ◽  
Carol R. Radinsky ◽  
Douglas Chyatte ◽  
Anthony J. Furlan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Lower Limit ◽  
Analysis Of Covariance ◽  
Control Group ◽  
Sprague Dawley ◽  
Doppler Flowmetry ◽  
Cranial Window ◽  
Time Control ◽  
Oxide Synthase

Variations in the height of the CBF response to hypotension have been described recently in normal animals. The authors evaluated the effects of nitric oxide synthase (NOS) inhibition on these variations in height using laser Doppler flowmetry in 42 anesthetized (halothane and N2O) male Sprague-Dawley rats prepared with a superfused closed cranial window. In four groups (time control, enantiomer control, NOS inhibition, and reinfusion control) exsanguination to MABPs from 100 to 40 mm Hg was used to produce autoregulatory curves. For each curve the lower limit of autoregulation (the MABP at the first decrease in CBF) was identified; the pattern of autoregulation was classified as “peak” (15% increase in %CBF), “classic” (plateau with a decrease at the lower limit of autoregulation), or “none” (15% decrease in %CBF); and the autoregulatory height as the %CBF at 70 mm Hg (%CBF70) was determined. NOS inhibition decreased %CBF70 in the NOS inhibition group (P = 0.014), in the control (combined time and enantiomer control) group (P = 0.015), and in the reinfusion control group (P = 0.025). NOS inhibition via superfusion depressed the autoregulatory pattern (P = 0.02, McNemar test on changes in autoregulatory pattern) compared with control (P = 0.375). Analysis of covariance showed that changes induced by NOS inhibition in the parameters of autoregulatory height are not related to changes in the lower limit, but are strongly (P < 0.001) related to each other. NOS inhibition depressed the autoregulatory pattern, decreasing the seemingly paradoxical increase in CBF as blood pressure decreases. These results suggest that nitric oxide increases CBF near the lower limit and augments the hypotensive portion of the autoregulatory curve.

scholarly journals Importance of Nitric Oxide Synthase Inhibition to the Attenuated Vascular Responses Induced by Topical L-Nitroarginine during Vibrissal Stimulation

1994 ◽  
Vol 14 (1) ◽  
pp. 45-48 ◽  
Author(s):  
Katsumi Irikura ◽  
Kenneth I. Maynard ◽  
Michael A. Moskowitz
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Enzyme Inhibition ◽  
Sprague Dawley ◽  
Somatosensory Stimulation ◽  
Cranial Window ◽  
Nos Inhibitors ◽  
Before And After ◽  
Cortical Gray Matter ◽  
Oxide Synthase

We assessed the regional cerebral blood flow (rCBF) response to vibrissal stimulation before and after nitric oxide synthase (NOS) inhibitors were topically applied through a closed cranial window placed over the cortical barrel fields in anesthetized Sprague–Dawley rats. In the presence of L-nitroarginine (1 m M), both the maximum and total responses became reduced, but only in those animals demonstrating >50% inhibition of NOS activity as determined by the conversion of [3H]arginine to [3H]citrulline within homogenates taken from cortical gray matter under the cranial window. The degree of enzyme inhibition depended in part, upon duration after topical application of NOS inhibitor. When >50%, enzyme inhibition correlated with the decrease in maximum and total rCBF response (p < 0.01). These findings emphasize the merits of assessing enzyme activity after administering NOS inhibitors, and suggest that NO generated from parenchymal NOS activity plays an important role in the cerebrovascular response to physiologic somatosensory stimulation under the stated conditions.

scholarly journals Muscle contraction induced arterial shear stress increases endothelial nitric oxide synthase phosphorylation in humans

2017 ◽  
Vol 313 (4) ◽  
pp. H854-H859 ◽  
Author(s):  
Darren P. Casey ◽  
Kenichi Ueda ◽  
Lauren Wegman-Points ◽  
Gary L. Pierce
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Brachial Artery ◽  
Endothelial Nitric Oxide Synthase ◽  
Control Group ◽  
Time Control ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Male Subjects

We determined if local increases in brachial artery shear during repetitive muscle contractions induce changes in protein expression of endothelial nitric oxide synthase (eNOS) and/or phosphorylated (p-)eNOS at Ser1177, the primary activation site on eNOS, in endothelial cells (ECs) of humans. Seven young male subjects (25 ± 1 yr) performed 20 separate bouts (3 min each) of rhythmic forearm exercise at 20% of maximum over a 2-h period. Each bout of exercise was separated by 3 min of rest. An additional six male subjects (24 ± 1 yr) served as time controls (no exercise). ECs were freshly isolated from the brachial artery using sterile J-wires through an arterial catheter at baseline and again after the 2-h exercise or time control period. Expression of eNOS or p-eNOS Ser1177 in ECs was determined via immunofluorescence. Brachial artery mean shear rate was elevated compared with baseline and the time control group throughout the 2-h exercise protocol ( P < 0.001). p-eNOS Ser1177 expression was increased 57% in ECs in the exercise group [0.06 ± 0.01 vs. 0.10 ± 0.02 arbitrary units (au), P = 0.02] but not in the time control group (0.08 ± 0.01 vs. 0.07 ± 0.01 au, P = 0.72). In contrast, total eNOS expression did not change in either the exercise (0.13 ± 0.04 vs. 0.12 ± 0.03 au) or time control (0.12 ± 0.03 vs. 0.11 ± 0.03 au) group ( P > 0.05 for both). Our novel results suggest that elevations in brachial artery shear increase eNOS Ser1177 phosphorylation in the absence of changes in total eNOS in ECs of young healthy male subjects, suggesting that this model is sufficient to alter posttranslational modification of eNOS activity in vivo in humans. NEW & NOTEWORTHY Elevations in brachial artery shear in response to forearm exercise increased endothelial nitric oxide synthase Ser1177 phosphorylation in brachial artery endothelial cells of healthy humans. Our present study provides the first evidence in humans that muscle contraction-induced increases in conduit arterial shear lead to in vivo posttranslational modification of endothelial nitric oxide synthase activity in endothelial cells.

scholarly journals The Role of Neuronal Nitric Oxide Synthase in Regulation of Cerebral Blood Flow in Normocapnia and Hypercapnia in Rats

1995 ◽  
Vol 15 (5) ◽  
pp. 774-778 ◽  
Author(s):  
Qiong Wang ◽  
Dale A. Pelligrino ◽  
Verna L. Baughman ◽  
Heidi M. Koenig ◽  
Ronald F. Albrecht
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Nitric Oxide Synthase ◽  
Inhibitory Action ◽  
Neuronal Nitric Oxide Synthase ◽  
Muscarinic Agonist ◽  
Doppler Flowmetry ◽  
Nos Inhibitors ◽  
Oxide Synthase

The nitric oxide synthase (NOS) inhibitors, nitro-L-arginine, its methyl ester, and N-monomethyl-L-arginine, have been shown to attenuate resting CBF and hypercapnia-induced cerebrovasodilation. Those agents nonspecifically inhibit the endothelial and neuronal NOS (eNOS and nNOS). In the present study, we used a novel nNOS inhibitor, 7-nitroindazole (7-NI) to examine the role of nNOS in CBF during normocapnia and hypercapnia in fentanyl/N2O-anesthetized rats. CBF was monitored using laser-Doppler flowmetry. Administration of 7-NI (80 mg kg−1 i.p.) reduced cortical brain NOS activity by 57%, the resting CBF by 19–27%, and the CBF response to hypercapnia by 60%. The 60% reduction was similar in magnitude to the CBF reductions observed in previous studies in which nonspecific NOS inhibitors were used. In the present study, 7-NI did not increase the MABP. Furthermore, the CBF response to oxotremorine, a blood–brain barrier permeant muscarinic agonist that induces cerebrovasodilation via endothelium-derived NO, was unaffected by 7-NI. These results confirmed that 7-NI does not influence eNOS; they also indicated that the effects of 7-NI on the resting CBF and on the CBF response to hypercapnia in this study were solely related to its inhibitory action on nNOS. The results further suggest that the NO synthesized by the action of nNOS participates in regulation of basal CBF and is the major, if not the only, category of NO contributing to the hypercapnic CBF response.

scholarly journals Preventive Effect of Lactobacillus Plantarum CQPC10 on Activated Carbon Induced Constipation in Institute of Cancer Research (ICR) Mice

2018 ◽  
Vol 8 (9) ◽  
pp. 1498 ◽  
Author(s):  
Jing Zhang ◽  
Xianrong Zhou ◽  
Benshou Chen ◽  
Xingyao Long ◽  
Jianfei Mu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Activated Carbon ◽  
Nitric Oxide Synthase ◽  
Lactobacillus Plantarum ◽  
Quantitative Polymerase Chain Reaction ◽  
Inhibitory Effect ◽  
Lactobacillus Bulgaricus ◽  
Control Group ◽  
Expression Levels ◽  
Oxide Synthase

Chinese Paocai is a traditional fermented food containing an abundance of beneficial microorganisms. In this study, the microorganisms in Szechwan Paocai were isolated and identified, and a strain of lactic acid bacteria (Lactobacillus plantarum CQPC10, LP-CQPC10) was found to exert an inhibitory effect on constipation. Microorganisms were isolated and identified via 16S rDNA. Activated carbon was used to induce constipation in a mouse model and the inhibitory effect of LP-CQPC10 on this induced constipation was investigated via both pathological sections and qPCR (quantitative polymerase chain reaction). A strain of Lactobacillus plantarum was identified and named LP-CQPC10. The obtained results showed that, as compared to the control group, LP-CQPC10 significantly inhibited the amount, weight, and water content of faeces. The defecation time of the first tarry stool was significantly shorter in LP-CQPC10 groups than in the control group. The activated carbon progradation rate was significantly higher when compared to the control group and the effectiveness was improved. LP-CQPC10 increased the serum levels of MTL (motilin), Gas (gastrin), ET (endothelin), AchE (acetylcholinesterase), SP (substance P), and VIP (vasoactive intestinal peptide), while decreasing the SS (somatostatin) level. Furthermore, it improved the GSH (glutathione) level and decreased the MPO (myeloperoxidase), MDA (malondialdehyde), and NO (nitric oxide) levels. The results of qPCR indicated that LP-CQPC10 significantly up-regulated the mRNA expression levels of c-Kit, SCF (stem cell factor), GDNF (glial cell-derived neurotrophic factor), eNOS (endothelial nitric oxide synthase), nNOS (neuronal nitric oxide synthase), and AQP3 (aquaporin-3), while down-regulating the expression levels of TRPV1 (transient receptor potential cation channel subfamily V member 1), iNOS (inducible nitric oxide synthase), and AQP9 (aquaporin-9). LP-CQPC10 showed a good inhibitory effect on experimentally induced constipation, and the obtained effectiveness is superior to that of Lactobacillus bulgaricus, indicating the better probiotic potential of this strain.

Neuronal nitric oxide synthase modulates rat renal microvascular function

1998 ◽  
Vol 274 (3) ◽  
pp. F516-F524 ◽  
Author(s):  
Atsuhiro Ichihara ◽  
Edward W. Inscho ◽  
John D. Imig ◽  
L. Gabriel Navar
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Neuronal Nitric Oxide Synthase ◽  
Macula Densa ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Vasoconstrictor Response ◽  
Arteriolar Tone ◽  
Oxide Synthase

This study was performed to determine the influence of neuronal nitric oxide synthase (nNOS) on renal arteriolar tone under conditions of normal, interrupted, and increased volume delivery to the macula densa segment and on the microvascular responses to angiotensin II (ANG II). Experiments were performed in vitro on afferent (21.2 ± 0.2 μm) and efferent (18.5 ± 0.2 μm) arterioles of kidneys harvested from male Sprague-Dawley rats, using the blood-perfused juxtamedullary nephron technique. Superfusion with the specific nNOS inhibitor, S-methyl-l-thiocitrulline (l-SMTC), decreased afferent and efferent arteriolar diameters, and these decreases in arteriolar diameters were prevented by interruption of distal volume delivery by papillectomy. When 10 mM acetazolamide was added to the blood perfusate to increase volume delivery to the macula densa segment, afferent arteriolar vasoconstrictor responses tol-SMTC were enhanced, but this effect was again completely prevented after papillectomy. In contrast, the arteriolar diameter responses to the nonselective NOS inhibitor, N ω-nitro-l-arginine (l-NNA) were only attenuated by papillectomy.l-SMTC (10 μM) enhanced the efferent arteriolar vasoconstrictor response to ANG II but did not alter the afferent arteriolar vasoconstrictor responsiveness to ANG II. In contrast, l-NNA (100 μM) enhanced both afferent and efferent arteriolar vasoconstrictor responses to ANG II. These results indicate that the modulating influence of nNOS on afferent arteriolar tone of juxtamedullary nephrons is dependent on distal tubular fluid flow. Furthermore, nNOS exerts a differential modulatory action on the juxtamedullary microvasculature by enhancing efferent, but not afferent, arteriolar responsiveness to ANG II.

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.

Effects of chronic inhibition of inducible nitric oxide synthase in hyperthyroid rats

2005 ◽  
Vol 288 (6) ◽  
pp. E1252-E1257 ◽  
Author(s):  
Isabel Rodríguez-Gómez ◽  
Rosemary Wangensteen ◽  
Juan Manuel Moreno ◽  
Virginia Chamorro ◽  
Antonio Osuna ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Control Group ◽  
Hemodynamic Variable ◽  
Male Wistar Rats ◽  
Oxide Synthase ◽  
Inos Inhibition ◽  
Inducible Nitric Oxide

We hypothesized that nitric oxide generated by inducible nitric oxide synthase (iNOS) may contribute to the homeostatic role of this agent in hyperthyroidism and may, therefore, participate in long-term control of blood pressure (BP). The effects of chronic iNOS inhibition by oral aminoguanidine (AG) administration on BP and morphological and renal variables in hyperthyroid rats were analyzed. The following four groups ( n = 8 each) of male Wistar rats were used: control group and groups treated with AG (50 mg·kg−1·day−1, via drinking water), thyroxine (T4, 50 μg·rat−1·day−1), or AG + T4. All treatments were maintained for 3 wk. Tail systolic BP and heart rate (HR) were recorded weekly. Finally, we measured BP (mmHg) and HR in conscious rats and morphological, plasma, and renal variables. T4 administration produced a small BP (125 ± 2, P < 0.05) increase vs. control (115 ± 2) rats. AG administration to normal rats did not modify BP (109 ± 3) or any other hemodynamic variable. However, coadministration of T4 and AG produced a marked increase in BP (140 ± 3, P < 0.01 vs. T4). Pulse pressure and HR were increased in both T4- and T4 + AG -treated groups without differences between them. Plasma NOx (μmol/l) were increased in the T4 group (10.02 ± 0.15, P < 0.05 vs. controls 6.1 ± 0.10), and AG reduced this variable in T4-treated rats (6.81 ± 0.14, P < 0.05 vs. T4) but not in normal rats (5.78 ± 0.20). Renal and ventricular hypertrophy and proteinuria of hyperthyroid rats were unaffected by AG treatment. In conclusion, the results of the present paper indicate that iNOS activity may counterbalance the prohypertensive effects of T4.

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.

scholarly journals Role of heme oxygenase-2 in pial arteriolar response to acetylcholine in mice with and without transfusion of cell-free hemoglobin polymers

2008 ◽  
Vol 295 (2) ◽  
pp. R498-R504 ◽  
Author(s):  
Xinyue Qin ◽  
Herman Kwansa ◽  
Enrico Bucci ◽  
Sylvain Doré ◽  
Darren Boehning ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Heme Oxygenase ◽  
Oxygen Carrier ◽  
Protoporphyrin Ix ◽  
Cranial Window ◽  
Dilatory Response ◽  
A Cell ◽  
Oxide Synthase

Carbon monoxide derived from heme oxygenase (HO) may participate in cerebrovascular regulation under specific circumstances. Previous work has shown that HO contributes to feline pial arteriolar dilation to acetylcholine after transfusion of a cell-free polymeric hemoglobin oxygen carrier. The role of constitutive HO2 in the pial arteriolar dilatory response to acetylcholine was determined by using 1) HO2-null mice (HO2−/−), 2) the HO inhibitor tin protoporphyrin IX (SnPPIX), and 3) 4,5,6,7-tetrabromobenzotriazole (TBB), an inhibitor of casein kinase-2 (CK2)-dependent phosphorylation of HO2. In anesthetized mice, superfusion of a cranial window with SnPPIX decreased arteriolar dilation produced by 10 μM acetylcholine by 51%. After partial polymeric hemoglobin exchange transfusion, the acetylcholine response was normal but was reduced 72% by SnPPIX and 95% by TBB. In HO2−/− mice, the acetylcholine response was modestly reduced by 14% compared with control mice and was unaffected by SnPPIX. After hemoglobin transfusion in HO2−/− mice, acetylcholine responses were also unaffected by SnPPIX and TBB. In contrast, nitric oxide synthase inhibition completely blocked the acetylcholine responses in hemoglobin-transfused HO2−/− mice. We conclude 1) that HO2 activity partially contributes to acetylcholine-induced pial arteriolar dilation in mice, 2) that this contribution is augmented in the presence of a plasma-based hemoglobin polymer and appears to depend on a CK2 kinase mechanism, 3) that nitric oxide synthase activity rather than HO1 activity contributes to the acetylcholine reactivity in HO2−/− mice, and 4) that plasma-based polymeric hemoglobin does not scavenge all of the nitric oxide generated by cerebrovascular acetylcholine stimulation.

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