Interaction between endogenously produced carbon monoxide and nitric oxide in regulation of renal afferent arterioles

2006 ◽  
Vol 291 (6) ◽  
pp. H2772-H2778 ◽  
Author(s):  
Fady T. Botros ◽  
L. Gabriel Navar
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Soluble Guanylate Cyclase ◽  
No Synthase ◽  
No Production ◽  
Heme Oxygenases ◽  
Juxtamedullary Nephron ◽  
Calcium Activated Potassium Channels ◽  
Afferent Arterioles ◽  
Stimulation Of

Heme oxygenases (HO-1 and HO-2) catalyze the conversion of heme to carbon monoxide (CO), iron, and biliverdin. CO causes vasorelaxation via stimulation of soluble guanylate cyclase (sGC) and/or activation of calcium-activated potassium channels. Because nitric oxide (NO) exerts effects via the same pathways, we tested the interaction between CO and NO on rat afferent arterioles (AAs) using the blood-perfused juxtamedullary nephron preparation. AAs were superfused with either tricarbonyldichlororuthenium (II) dimer, known as CO releasing molecule (CORM-2), 10 μmol/l CO solution, or 15 μmol/l chromium mesoporphyrin (CrMP, HO inhibitor). AAs were also superfused with 1 mmol/l Nω-nitro-l-arginine (l-NNA) to inhibit NO synthase (NOS) or 10 μmol/l 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one to inhibit sGC, and then CrMP was superfused during NOS inhibition or sGC inhibition. Treatment with 150 and 300 μmol/l CORM-2 or with CO (10 μmol/l) significantly dilated AAs (22.0 ± 0.9 and 22.8 ± 0.9 vs. 18.3 ± 0.9 μm, n = 5, P < 0.05; and 26.0 ± 1.4 vs. 18.8 ± 0.7 μm, n = 5, P < 0.05). In untreated vessels, HO inhibition did not alter AA diameter (17.5 ± 0.7 vs. 17.2 ± 0.6 μm, n = 7, P > 0.05); however, during inhibition of NO production, which constricted arterioles to 14.6 ± 1.2 μm, n = 6, P < 0.05, concurrent HO inhibition led to further vasoconstriction (11.7 ± 1.6 μm, n = 6, P < 0.05). CORM-2 attenuated the l-NNA-induced vasoconstriction. Inhibition of sGC caused significant constriction (15.7 ± 0.4 vs. 18.8 ± 0.4 μm, n = 6, P < 0.05). HO inhibition during sGC inhibition did not cause further change in AAs (15.5 ± 0.7 μm, n = 6). We conclude that endogenously produced CO does not exert a perceptible influence on AA diameter in the presence of intact NO system; however, when NO production is inhibited, CO serves as an important renoprotective reserve mechanism to prevent excess afferent arteriolar constriction.

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.

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.

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

1998 ◽  
Vol 5 (6) ◽  
pp. 467-480
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 of 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.

scholarly journals In Endothelial Cells, the Activation or Stimulation of Soluble Guanylyl Cyclase Induces the Nitric Oxide Production by a Mechanism Dependent of Nitric Oxide Synthase Activation

2018 ◽  
Vol 21 ◽  
pp. 38-45 ◽  
Author(s):  
Ariane Migliato Martinelli ◽  
Carla Nascimento dos Santos Rodrigues ◽  
Thiago Francisco de Moraes ◽  
Gerson Jhonatan Rodrigues
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Nitric Oxide Synthase ◽  
Soluble Guanylate Cyclase ◽  
Soluble Guanylyl Cyclase ◽  
No Production ◽  
Selective Electrode ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Stimulation Of

Purpose. In endothelial cells, investigate if the soluble guanylate cyclase (sGC) activation or stimulation is able to potentiate the relaxation in vessels. Methods. Aortic and coronary rings with and without endothelium were placed in a myograph and cumulative concentration-effect curves for DETA-NO or ataciguat were performed. Nitric oxide (NO) were measured by fluorescence or by selective electrode in human umbilical endothelial cells (HUVECs) in response to some treatments, including ataciguat, 8-Br-cGMP and A23187. Results. The presence of the endothelium potentiated the relaxation induced by DETA-NO in aortic and coronary rings. In addition, in aortic rings the endothelium potentiated the relaxation induced by ataciguat. In the presence of nitric oxide synthase (NOS) inhibitor, the endothelium effect was abolished to DETA-NO or ataciguat, in both vessels. Ataciguat, 8-Br-cGMP and A23187 were able to induce NO production in HUVECs cells. In the presence of NOS inhibitor, the NO production induced by ataciguat and 8-Br-cGMP was abolished. Conclusions. Our results suggest that in aortic and coronary rings the endothelium potentiates the relaxation induced by activation or stimulation of sGC through a mechanism dependent of NOS activation. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Nitric oxide increases carbon monoxide production by piglet cerebral microvessels

2005 ◽  
Vol 289 (4) ◽  
pp. H1442-H1447 ◽  
Author(s):  
Charles W. Leffler ◽  
Liliya Balabanova ◽  
Alexander L. Fedinec ◽  
Helena Parfenova
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Catalytic Activity ◽  
Excitatory Amino Acid ◽  
Gas Chromatography Mass Spectrometry ◽  
No Production ◽  
No Donor ◽  
Cerebral Microvessels ◽  
Stimulation Of

Carbon monoxide (CO) and nitric oxide (NO) can be involved in the regulation of cerebral circulation. Inhibition of production of either one of these gaseous intercellular messengers inhibits newborn pig cerebral arteriolar dilation to the excitatory amino acid glutamate. Glutamate can increase NO production. Therefore, the present study tests the hypothesis that NO, which is increased by glutamate, stimulates the production of CO by cerebral microvessels. Experiments used freshly isolated cerebral microvessels from piglets that express only heme oxygenase-2 (HO-2). CO production was measured by gas chromatography-mass spectrometry. Although inhibition of nitric oxide synthase (NOS) with Nω-nitro-l-arginine (l-NNA) did not alter basal HO-2 catalytic activity or CO production, l-NNA blocked glutamate stimulation of HO-2 activity and CO production. Furthermore, the NO donor sodium nitroprusside mimicked the actions of glutamate on HO-2 and CO production. The action of NO appears to be via cGMP because 8-bromo-cGMP mimics and 1 H-[1,2,4]oxadiazole-[4,3- a]quinoxalin-1-one (ODQ) blocks glutamate stimulation of CO production and HO-2 catalytic activity. Inhibitors of neither casein kinase nor phosphotidylinositol 3-kinase altered HO-2 catalytic activity. Conversely, inhibition of calmodulin with calmidazolium chloride blocked glutamate stimulation of CO production and reduced HO-2 catalytic activity. These data suggest that glutamate may activate NOS producing NO that leads to CO synthesis via a cGMP-dependent elevation of HO-2 catalytic activity. These results are consistent with the findings in vivo that either HO or NOS inhibition blocks cerebrovascular dilation to glutamate in piglets.

scholarly journals Nitric oxide and renal and cardiac dysfunction in cirrhosis

2002 ◽  
Vol 102 (2) ◽  
pp. 213-222 ◽  
Author(s):  
Joaquín GARCÍA-ESTAÑ ◽  
M. Clara ORTIZ ◽  
Samuel S. LEE
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Cardiac Dysfunction ◽  
Cardiac Contractility ◽  
No Synthase ◽  
No Production ◽  
Ventricular Contractility ◽  
Cirrhotic Cardiomyopathy ◽  
Water Excretion ◽  
Enhanced Production

Nitric oxide (NO) has diverse physiological and pathophysiological effects. The roles of NO in the renal and cardiac dysfunction found in cirrhosis are reviewed. In the kidneys of experimental animals with cirrhosis, several lines of evidence speak in favour of an enhanced production of NO, through the activation of both endothelial constitutive and inducible isoforms of NO synthase. In contrast with the situation in normal animals, inhibition of NO synthesis in rats with cirrhosis improves sodium and water excretion via blood pressure-dependent and -independent mechanisms, which indicates that the renal sodium and water retention of cirrhosis is related to an excess of NO production. The deleterious effect of excessive NO on the kidney may be mediated by peroxynitrite, a potent oxidant that is readily formed whenever superoxide anions and the ·NO radical are produced together. The peroxidation of arachidonic acid by peroxynitrite leads to the formation of F2a-isoprostanes, which are powerful renal vasoconstrictors. F2a-isoprostane levels are correlated with the severity of liver injury during cirrhosis. However, whether peroxynitrite or F2a-isoprostanes are the elusive mediator of the NO-induced renal alterations in cirrhosis remains to be firmly established. NO is also involved in cardiac contractility, probably in the normal heart as well as in disease conditions such as non-cirrhotic and cirrhotic cardiomyopathy. In the latter state, evidence suggests that inducible NO synthase attenuates ventricular contractility, mediated by cGMP. Another gas that transduces its signal through cGMP, carbon monoxide, is also likely to play a role in cirrhotic cardiomyopathy, but the nature of the interaction between NO and carbon monoxide in this syndrome remains unclear.

Basal nitric oxide production curtails arteriolar vasoconstrictor responses to ANG II in rat kidney

1996 ◽  
Vol 271 (2) ◽  
pp. F365-F373 ◽  
Author(s):  
H. Ikenaga ◽  
R. W. Fallet ◽  
P. K. Carmines
Keyword(s):  
Nitric Oxide ◽  
Rat Kidney ◽  
No Synthase ◽  
Ang Ii ◽  
Juxtamedullary Nephron ◽  
Endogenous Nitric Oxide ◽  
Synthase Inhibitor ◽  
Baseline Diameter ◽  
Stimulation Of

Experiments were performed to test the hypothesis that renal arteriolar vasoconstrictor responses to angiotensin II (ANG II) are curtailed through a mechanism that involves stimulation of endogenous nitric oxide (NO) synthesis. The in vitro blood-perfused juxtamedullary nephron technique was exploited to monitor arteriolar lumen diameter responses to exogenous ANG II before and during treatment with the NO synthase inhibitor N omega-nitro-L-arginine (L-NNA). Under control conditions, 1 nM ANG II reduced afferent and efferent arteriolar diameters by 13 and 11%, respectively. In the presence of L-NNA, 1 nM ANG II decreased afferent diameter by 26% and efferent diameter by 35%. This augmentation could not be attributed to the L-NNA-induced decrease in baseline diameter. L-NNA also augmented vasopressin responses, indicating a lack of agonist specificity in this interaction. ANG II reactivity during L-NNA treatment was not enhanced when tissue NO activity was fixed at basal levels (exposure to 1 microM sodium nitroprusside). These results indicate that endogenous NO modulates the vasoconstrictive impact of ANG II on both afferent and efferent arterioles of juxtamedullary nephrons and that this process does not require stimulation of NO synthesis.

Neuropeptide stimulation of the nitric oxide signaling pathway in Drosophila melanogaster Malpighian tubules

1997 ◽  
Vol 273 (2) ◽  
pp. R823-R827 ◽  
Author(s):  
S. A. Davies ◽  
E. J. Stewart ◽  
G. R. Huesmann ◽  
N. J. Skaer ◽  
S. H. Maddrell ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Drosophila Melanogaster ◽  
Signaling Pathway ◽  
Guanylate Cyclase ◽  
Soluble Guanylate Cyclase ◽  
Fluid Secretion ◽  
Malpighian Tubules ◽  
No Production ◽  
Intracellular Cgmp ◽  
Stimulation Of

Activation of the nitric oxide (NO) and guanosine 3', 5'-cyclic monophosphate (cGMP) signaling pathway stimulates fluid secretion by the Drosophila melanogaster Malpighian tubule. The neuropeptide cardioacceleratory peptide 2b (CAP2b) has been previously shown to stimulate fluid secretion in this epithelium by elevating intracellular cGMP levels. Therefore, it was of interest to investigate if CAP2b acts through NO in isolated tubules and thus presumably through stimulation of a tubule NO synthase (NOS). We show here by reverse-transcription polymerase chain reaction that Drosophila NOS (dNOS) is expressed in Malpighian tubules. Biochemical assays of NOS activity in whole tubules show that CAP2b significantly stimulates NOS activity. Additionally, fluid secretion and cyclic nucleotide assays show that CAP2b-induced elevation of intracellular cGMP levels and fluid secretion rates are dependent on the activation of a soluble guanylate cyclase. Treatment of tubules with a specific NOS inhibitor abolishes the CAP2b-induced rise in intracellular cGMP levels. These data indicate that CAP2b stimulates NOS and therefore, endogenous NO production, which, in turn, stimulates a soluble guanylate cyclase. This is the first demonstration of stimulation of an endogenous NOS by a defined peptide in Drosophila.

scholarly journals Rise in endothelium-derived NO after stimulation of rat perivascular sympathetic mesenteric nerves

1999 ◽  
Vol 277 (3) ◽  
pp. H1027-H1035 ◽  
Author(s):  
Mauricio P. Boric ◽  
Xavier F. Figueroa ◽  
M. Verónica Donoso ◽  
Alfonso Paredes ◽  
Inés Poblete ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Electrical Stimulation ◽  
Sympathetic Activity ◽  
Perfusion Pressure ◽  
Stimulus Frequency ◽  
No Synthase ◽  
No Production ◽  
No Release ◽  
Perivascular Nerves ◽  
Stimulation Of

To evaluate whether sympathetic activity induces nitric oxide (NO) production, we perfused the rat arterial mesenteric bed and measured luminally accessible norepinephrine (NE), NO, and cGMP before, during, and after stimulation of perivascular nerves. Electrical stimulation (1 min, 30 Hz) raised perfusion pressure by 97 ± 7 mmHg, accompanied by peaks of 23 ± 3 pmol NE, 445 ± 48 pmol NO, and 1 pmol cGMP. Likewise, perfusion with 10 μM NE induced vasoconstriction coupled to increased NO and cGMP release. Electrically elicited NO release depended on stimulus frequency and duration. Endothelium denudation with saponin abolished the NO peak without changing NE release. Inhibition of NO synthase with 100 μM N ω-nitro-l-arginine reduced basal NO and cGMP release and blocked the electrically stimulated and exogenous NE-stimulated NO peak while enhancing vasoconstriction. Blocking either sympathetic exocytosis with 1 μM guanethidine or α1-adrenoceptors with 30 nM prazosin abolished the electrically evoked vasoconstriction and NO release. α2-Adrenoceptor blockade with 1 μM yohimbine reduced both vasoconstriction and NO peak while increasing NE release. In summary, sympathetically released NE induces vasoconstriction, which triggers a secondary release of endothelial NO coupled to cGMP production.

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