Role of neuronal NO synthase in relationship between NO and opioids in hypoxia-induced pial artery dilation

1997 ◽  
Vol 273 (4) ◽  
pp. H1807-H1815 ◽  
Author(s):  
M. J. Wilderman ◽  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Sodium Salt ◽  
No Synthase ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Pial Artery ◽  
Nos Inhibitor ◽  
Neuronal Nos

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, via the formation of guanosine 3′,5′-cyclic monophosphate (cGMP) and subsequent release of Met-enkephalin and Leu-enkephalin in the newborn pig. In separate studies, these opioids were also observed to elicit NO-dependent pial dilation. The present study was designed to investigate the role of the neuronal isoform of NO synthase (NOS) in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. Tetrodotoxin (10−6 M) attenuated the dilation resulting from hypoxia ([Formula: see text]∼35 mmHg; 25 ± 1 vs. 14 ± 1%). Similarly, 7-nitroindazole, sodium salt (7-NINA, 10−6M), a purported neuronal NOS inhibitor, attenuated hypoxic pial dilation (26 ± 1 vs. 14 ± 2%). Hypoxic dilation was accompanied by elevated cerebrospinal (CSF) cGMP, which was blocked by 7-NINA (433 ± 19 and 983 ± 36 vs. 432 ± 19 and 441 ± 19 fmol/ml for control and hypoxia in absence and presence of 7-NINA, respectively). Additionally, hypoxic dilation was also accompanied by elevated CSF Met-enkephalin, which was attenuated by 7-NINA (1,027 ± 47 and 2,871 ± 134 vs. 779 ± 78 and 1,551 ± 42 pg/ml for control and hypoxia in absence and presence of 7-NINA, respectively). In contrast, Met-enkephalin (10−10, 10−8, and 10−6 M) induced dilation that was unchanged by 7-NINA (7 ± 1, 12 ± 1, and 18 ± 1 vs. 6 ± 1, 10 ± 1, and 17 ± 1%, respectively). N-methyl-d-aspartate (NMDA, 10−8 and 10−6 M), an activator of neuronal NOS, induced pial dilation that was blocked by 7-NINA (10 ± 1 and 20 ± 2 vs. 1 ± 1 and 2 ± 1%, respectively). However, sodium nitroprusside-induced dilation was unchanged by 7-NINA. These data indicate that neuronal NOS contributes to hypoxic pial artery dilation but not to opioid-induced dilation. Furthermore, these data suggest that neuronally derived NO contributes to hypoxic dilation, at least in part, via formation of cGMP and the subsequent release of opioids.

Role of nitric oxide and cAMP in prostaglandin-induced pial arterial vasodilation

1995 ◽  
Vol 268 (4) ◽  
pp. H1436-H1440 ◽  
Author(s):  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Topical Administration ◽  
No Donor ◽  
Cyclic Monophosphate ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Arterial Dilation ◽  
Synthase Inhibitor

The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to prostaglandin (PG)I2 and PGE2 in newborn pigs equipped with a closed cranial window. PGI2 (1–100 ng/ml) produced pial arterial dilation that was blunted by nitro-L-arginine (L-NNA, 10(-6) M), an NO synthase inhibitor (9 +/- 1 vs. 2 +/- 1%, 21 +/- 1 vs. 5 +/- 3% for 1 and 100 ng/ml PGI2 respectively, n = 6; means +/- SE). PGI2-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in cGMP were blocked by L-NNA (386 +/- 8 and 1,054 +/- 30 fmol/ml vs. 266 +/- 6 and 274 +/- 4 fmol/ml for control and PGI2 100 ng/ml before and after L-NNA respectively, n = 6). In contrast, PGI2-associated changes in CSF cAMP were unchanged by L-NNA (1,021 +/- 25 and 2,703 +/- 129 fmol/ml vs. 980 +/- 23 and 2,636 +/- 193 fmol/ml for control, PGI2 100 ng/ml before and after L-NNA, respectively, n = 6). PGE2 elicited similar changes in pial artery diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also being similarly inhibited by L-NNA. After L-NNA, topical administration of the NO donor sodium nitroprusside (SNP, 10(-9) M) increased pial artery diameter up to the resting level before L-NNA and partially restored the vasodilation elicited by PGI2 and PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of nitric oxide and cAMP in beta-adrenoceptor-induced pial artery vasodilation

1995 ◽  
Vol 268 (3) ◽  
pp. H1071-H1076 ◽  
Author(s):  
S. Rebich ◽  
J. O. Devine ◽  
W. M. Armstead
Keyword(s):  
Nitric Oxide ◽  
Beta Agonist ◽  
Cyclic Monophosphate ◽  
Beta Adrenoceptor ◽  
Cranial Window ◽  
Pial Artery ◽  
Before And After ◽  
Adrenoceptor Agonists ◽  
Synthase Inhibitor

The present study was designed to investigate the role of nitric oxide (NO), guanosine 3',5'-cyclic monophosphate (cGMP), and adenosine 3',5'-cyclic monophosphate (cAMP) in the vasodilator response to beta-adrenoceptor agonists in newborn pigs equipped with a closed cranial window. Dobutamine (10(-8) and 10(-6) M), a beta 1-agonist, produced pial artery dilation that was blunted by NG-nitro-L-arginine (L-NNA; 10(-6) M), a NO synthase inhibitor (12 +/- 1 vs. 0 +/- 2% and 24 +/- 3 vs. 4 +/- 1% for 10(-8) and 10(-6) M dobutamine, respectively). Dobutamine-induced vasodilation was associated with increased cortical periarachnoid cerebrospinal fluid (CSF) cGMP, and these changes in CSF cGMP were blocked by L-NNA (391 +/- 10 and 675 +/- 36 fmol/ml vs. 307 +/- 3 and 346 +/- 37 fmol/ml for control and 10(-6) M dobutamine before and after L-NNA, respectively). In contrast, dobutamine-associated changes in CSF cAMP were unchanged by L-NNA (1,108 +/- 56 and 2,623 +/- 139 fmol/ml vs. 1,059 +/- 24 and 2,500 +/- 61 fmol/ml for control and 10(-6) M dobutamine before and after L-NNA, respectively). Salbutamol, a beta 2-agonist, and isoproterenol, a nonselective beta-agonist, elicited similar changes in pial diameter and cyclic nucleotides; vasodilation and changes in CSF cGMP also were similarly inhibited by L-NNA.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Role of Endothelial Nitric Oxide Synthase in Hypoxia-Induced Pial Artery Dilation

1998 ◽  
Vol 18 (5) ◽  
pp. 531-538 ◽  
Author(s):  
Michael J. Wilderman ◽  
William M. Armstead
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Methionine Enkephalin ◽  
Cranial Window ◽  
Pial Artery ◽  
Endothelial No Synthase ◽  
Before And After ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Nitric oxide (NO) contributes to hypoxia-induced pial artery dilation, at least in part, through the formation of cGMP and the subsequent release of methionine enkephalin and leucine enkephalin in the newborn pig. In separate studies, these opioids also were observed to elicit NO-dependent pial artery dilation, whereas light/dye endothelial injury reduced hypoxic pial dilation. The current study was designed to investigate the role of the endothelial isoform of NO synthase in hypoxic pial dilation, associated opioid release, and opioid dilation in piglets equipped with a closed cranial window. N-iminoethyl-l-ornithine (l-NIO) (10−6 mol/L), an antagonist that may have greater endothelial NO synthase inhibitory selectivity, had no effect on dilation elicited by hypoxia (Po2 ≈ 35 mm Hg) (24 ± 2 versus 24 ± 2% in the absence and presence of l-NIO, respectively, n = 8). Hypoxic dilation was accompanied by increased CSF cGMP, which also was unchanged in the presence of l-NIO (394 ± 19 and 776 ± 63 versus 323 ± 13 and 739 ± 25 fmol/mL for control and hypoxia in the absence and presence of l-NIO, respectively, n = 6). Additionally, hypoxic pial dilation was associated with increased CSF methionine enkephalin, which also was unchanged in the presence of l-NIO (992 ± 73 and 2469 ± 197 versus 984 ± 18 and 2275 ± 185 pg/mL, respectively, n = 6). In contrast, methionine enkephalin–induced dilation was blocked by l-NIO (6 ± 1, 10 ± 1, and 16 ± 1 versus 1 ± 1, 1 ± 1, and 2 ± 1% for 10−10, 10−8, 10−6 mol/L methionine enkephalin, respectively, before and after l-NIO, n = 8). Substance P–induced pial dilation was blunted by l-NIO, whereas responses to sodium nitroprusside and N-methyl-d-aspartate were unchanged. These data indicate that endothelial NO synthase contributes to opioid-induced pial artery dilation but not hypoxia-induced dilation. Additionally, these data suggest that neuronally derived NO contributes to hypoxic pial dilation.

scholarly journals Gastrointestinal nitric oxide generation in germ-free and conventional rats

2004 ◽  
Vol 287 (5) ◽  
pp. G993-G997 ◽  
Author(s):  
Tanja Sobko ◽  
Claudia Reinders ◽  
Elisabeth Norin ◽  
Tore Midtvedt ◽  
Lars E. Gustafsson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Gastrointestinal Tract ◽  
Intestinal Microflora ◽  
No Synthase ◽  
No Production ◽  
Germ Free ◽  
Qualitative And Quantitative ◽  
Nitrate Load ◽  
Nos Inhibitor

Nitric oxide (NO) is a central mediator of various physiological events in the gastrointestinal tract. The influence of the intestinal microflora for NO production in the gut is unknown. Bacteria could contribute to this production either by stimulating the mucosa to produce NO, or they could generate NO themselves. Using germ-free and conventional rats, we measured gaseous NO directly in the gastrointestinal tract and from the luminal contents using a chemiluminescence technique. Mucosal NO production was studied by using an NO synthase (NOS) inhibitor, and to evaluate microbial contribution to the NO generation, nitrate was given to the animals. In conventional rats, luminal NO differed profoundly along the gastrointestinal tract with the greatest concentrations in the stomach [>4,000 parts per billion (ppb)] and cecum (≈200 ppb) and lower concentrations in the small intestine and colon (≤20 ppb). Cecal NO correlated with the levels in incubated luminal contents. NOS inhibition lowered NO levels in the colon, without affecting NO in the stomach and in the cecum. Gastric NO increased greatly after a nitrate load, proving it to be a substrate for NO generation. In germ-free rats, NO was low (≤30 ppb) throughout the gastrointestinal tract and absent in the incubated luminal contents. NO also remained low after a nitrate load. Our results demonstrate a pivotal role of the intestinal microflora in gastrointestinal NO generation. Distinctly compartmentalized qualitative and quantitative NO levels in conventional and germ-free rats reflect complex host microbial cross talks, possibly making NO a regulator of the intestinal eco system.

scholarly journals Role of nitric oxide in the vascular effects of local warming of the skin in humans

1999 ◽  
Vol 86 (4) ◽  
pp. 1185-1190 ◽  
Author(s):  
D. L. Kellogg ◽  
Y. Liu ◽  
I. F. Kosiba ◽  
D. O’Donnell
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Control Period ◽  
No Synthase ◽  
Vascular Effects ◽  
Doppler Flowmetry ◽  
Cutaneous Vasodilation ◽  
Local Warming ◽  
Cutaneous Vascular Conductance

Local warming of skin induces vasodilation by unknown mechanisms. To test whether nitric oxide (NO) is involved, we examined effects of NO synthase (NOS) inhibition with N G-nitro-l-arginine methyl ester (l-NAME) on vasodilation induced by local warming of skin in six subjects. Two adjacent sites on the forearm were instrumented with intradermal microdialysis probes for delivery ofl-NAME and sodium nitroprusside. Skin blood flow was monitored by laser-Doppler flowmetry (LDF) at microdialysis sites. Local temperature (Tloc) of the skin at both sites was controlled with special LDF probe holders. Mean arterial pressure (MAP; Finapres) was measured and cutaneous vascular conductance calculated (CVC = LDF/MAP = mV/mmHg). Data collection began with a control period (Tloc at both sites = 34°C). One site was then warmed to 41°C while the second was maintained at 34°C. Local warming increased CVC from 1.44 ± 0.41 to 4.28 ± 0.60 mV/mmHg ( P < 0.05). Subsequent l-NAME administration reduced CVC to 2.28 ± 0.47 mV/mmHg ( P < 0.05 vs. heating), despite the continued elevation of Tloc. At a Tloc of 34°C,l-NAME reduced CVC from 1.17 ± 0.23 to 0.75 ± 0.11 mV/mmHg ( P < 0.05). Administration of sodium nitroprusside increased CVC to levels no different from those induced by local warming. Thus NOS inhibition attenuated, and sodium nitroprusside restored, the cutaneous vasodilation induced by elevation of Tloc; therefore, the mechanism of cutaneous vasodilation by local warming requires NOS generation of NO.

The role of nitric oxide in the regulation of the electrical activity of the trigeminal nerve in the rat

2021 ◽  
Author(s):  
S.O. Svitko ◽  
K.S. Koroleva ◽  
G.F. Sitdikova ◽  
K.A. Petrova
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Trigeminal Nerve ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
The Body ◽  
No Donor ◽  
No Signaling

Nitric oxide (NO) is a gaseous signaling molecule that regulates a number of physiological functions, including its role in the formation of migraine has been established. NO is endogenously produced in the body from L-arginine by NO synthase. The NO donor, nitroglycerin, is a trigger of migraine in humans and is widely used in the modeling of this disease in animals, which suggests the involvement of components of the NO signaling cascade in the pathogenesis of migraine. Based on the results obtained, it was found that an increase in the concentration of both the substrate for the synthesis of NO, L-arginine, and the NO donor, sodium nitroprusside, has a pro-nociceptive effect in the afferents of the trigeminal nerve. In this case, the effect of sodium nitroprusside is associated with the activation of intracellular soluble guanylate cyclase. Key words: nitric oxide, migraine, trigeminal nerve, L-arginine, guanylate cyclase, sodium nitroprusside, nociception.

Role of nitric oxide-derived oxidants in vascular injury from carbon monoxide in the rat

1999 ◽  
Vol 276 (3) ◽  
pp. H984-H992 ◽  
Author(s):  
Stephen R. Thom ◽  
Donald Fisher ◽  
Y. Anne Xu ◽  
Sarah Garner ◽  
Harry Ischiropoulos
Keyword(s):  
Nitric Oxide ◽  
Vessel Wall ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
No Synthase ◽  
Endothelial Lining ◽  
Nos Inhibitor ◽  
Vascular Status ◽  
Co Concentrations

Studies were conducted with rats to investigate whether exposure to CO at concentrations frequently found in the environment caused nitric oxide (NO)-mediated vessel wall changes. Exposure to CO at concentrations of 50 parts per million or higher for 1 h increased the concentration of nitrotyrosine in the aorta. Immunologically reactive nitrotyrosine was localized in a discrete fashion along the endothelial lining, and this was inhibited by pretreatment with the NO synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester (l-NAME). The CO-induced elevations of aortic nitrotyrosine were not altered by neutropenia or thrombocytopenia, and CO caused no change in the concentration of endothelial NOS. Consequences from NO-derived stress on the vasculature included an enhanced transcapillary efflux of albumin within the first 3 h after CO exposure and leukocyte sequestration that became apparent 18 h after CO exposure. Oxidized plasma low-density lipoprotein was found immediately after CO exposure, but this was not inhibited byl-NAME pretreatment. We conclude that exposure to relatively low CO concentrations can alter vascular status by several mechanisms and that many changes are linked to NO-derived oxidants.

scholarly journals Role of ETB receptors and nitric oxide in adrenal catecholamine secretion in anesthetized dogs

1999 ◽  
Vol 277 (4) ◽  
pp. R1051-R1056 ◽  
Author(s):  
Akio Hosokawa ◽  
Takahiro Nagayama ◽  
Kimiya Masada ◽  
Makoto Yoshida ◽  
Mizue Suzuki-Kusaba ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Splanchnic Nerve ◽  
Inhibitory Effect ◽  
Catecholamine Secretion ◽  
Anesthetized Dogs ◽  
Nos Inhibitor ◽  
Neuronal Nos ◽  
Endothelin B ◽  
Oxide Synthase

We examined the effects of sarafotoxin 6c (S6c), an endothelin-B (ETB) receptor agonist, on adrenal catecholamine secretion in response to cholinergic stimuli in pentobarbital sodium-anesthetized dogs. Drugs were administered intra-arterially into the adrenal gland through the phrenicoabdominal artery. Infusion of S6c attenuated increases in adrenal catecholamine output induced by splanchnic nerve stimulation. The inhibitory effect of S6c on the catecholamine secretion response was suppressed with a selective ETB receptor antagonist N- cis2,6-dimethylpiperidinocarbonyl-l-γ-methylleucyl-d-1-methoxycarbonyltryptophanyl-d-norleucine (BQ-788), a nitric oxide synthase (NOS) inhibitor N ω-nitro-l-arginine methyl ester, and a neuronal NOS inhibitor 7-nitroindazole monosodium salt (7-NINA). Similar results were obtained with the catecholamine secretion response induced by injection of ACh. 7-NINA alone did not affect these catecholamine secretion responses. These results suggest that ETB receptors play an inhibitory role in adrenal catecholamine secretion by activating neuronal NOS, whereas neuronal NOS is unlikely to be involved in regulation of adrenal catecholamine secretion in the absence of simultaneous ETB receptor stimulation.

scholarly journals Nitric oxide: a modulator, but not a mediator, of neurovascular coupling in rat somatosensory cortex

1999 ◽  
Vol 277 (2) ◽  
pp. H799-H811 ◽  
Author(s):  
Ute Lindauer ◽  
Dirk Megow ◽  
Hiroshi Matsuda ◽  
Ulrich Dirnagl
Keyword(s):  
Nitric Oxide ◽  
Somatosensory Cortex ◽  
Soluble Guanylyl Cyclase ◽  
No Synthase ◽  
Neuronal Activation ◽  
Regional Cerebral Blood ◽  
No Donors ◽  
Neuronal Nos ◽  
Rat Somatosensory Cortex

We investigated the role of nitric oxide (NO)/cGMP in the coupling of neuronal activation to regional cerebral blood flow (rCBF) in α-chloralose-anesthetized rats. Whisker deflection (60 s) increased rCBF by 18 ± 3%. NO synthase (NOS) inhibition by N ω-nitro-l-arginine (l-NNA; topically) reduced the rCBF response to 9 ± 4% and resting rCBF to 80 ± 8%. NO donors [ S-nitroso- N-acetylpenicillamine (SNAP; 50 μM), 3-morpholinosydnonimine (10 μM)] or 8-bromoguanosine 3′,5′-cyclic-monophosphate (8-BrcGMP; 100 μM)] restored resting rCBF andl-NNA-induced attenuation of the whisker response in the presence ofl-NNA, whereas the NO-independent vasodilator papaverine (1 mM) had no effect on the whisker response. Basal cGMP levels were decreased to 35% byl-NNA and restored to 65% of control by subsequent SNAP superfusion. Inhibition of neuronal NOS by 7-nitroindazole (7-NI; 40 mg/kg ip) or soluble guanylyl cyclase by 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 100 μM) significantly reduced resting rCBF to 86 ± 8 and 92 ± 10% and whisker rCBF response to 7 ± 4 and 12 ± 3%, respectively. ODQ reduced tissue cGMP to 54%. 8-BrcGMP restored the whisker response in the presence of 7-NI or ODQ. We conclude that NO, produced by neuronal NOS, is a modulator in the coupling of neuronal activation and rCBF in rat somatosensory cortex and that this effect is mainly mediated by cGMP.l-NNA-induced vasomotion was significantly reduced during increased neuronal activity and after restoration of basal NO levels, but not after restoration of cGMP.

Differential effects of l-NAME on rat venular hydraulic conductivity

2000 ◽  
Vol 279 (4) ◽  
pp. H2017-H2023 ◽  
Author(s):  
Rolando E. Rumbaut ◽  
Jianjie Wang ◽  
Virginia H. Huxley
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Methyl Ester ◽  
Hydraulic Conductivity ◽  
No Synthase ◽  
Vascular Effects ◽  
Nos Inhibitors ◽  
Before And After ◽  
Nos Inhibitor

The role of nitric oxide (NO) in microvascular permeability remains unclear because both increases and decreases in permeability by NO synthase (NOS) inhibitors have been reported. We sought to determine whether blood-borne constituents modify venular permeability responses to the NOS inhibitor N G-nitro-l-arginine methyl ester (l-NAME). We assessed hydraulic conductivity ( L p) of pipette-perfused rat mesenteric venules before and after exposure to 10−4 M l-NAME. In the absence of blood-borne constituents, l-NAME reduced L p by nearly 50% (from a median of 2.4 × 10−7cm · s−1 · cmH2O−1, n = 17, P < 0.001). The reduction in L p by l-NAME was inhibited by a 10-fold molar excess of l-arginine but notd-arginine ( n = 6). In a separate group of venules, blood flow was allowed to resume during exposure tol-NAME. In vessels perfused by blood duringl-NAME exposure, L p increased by 78% (from 1.4 × 10−7cm · s−1 · cmH2O−1, n = 10, P < 0.01). N G-nitro-d-arginine methyl ester did not affect L p in either of the two groups. These data imply that NO has direct vascular effects on permeability that are opposed by secondary changes in permeability mediated by blood-borne constituents.

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