Carbon monoxide promotes endothelium-dependent constriction of isolated gracilis muscle arterioles

2003 ◽  
Vol 285 (3) ◽  
pp. R536-R541 ◽  
Author(s):  
Fruzsina K. Johnson ◽  
Robert A. Johnson
Keyword(s):  
Carbon Monoxide ◽  
Methyl Ester ◽  
Aminolevulinic Acid ◽  
No Synthase ◽  
Gracilis Muscle ◽  
Sprague Dawley ◽  
No Donor ◽  
First Order ◽  
No Formation ◽  
Sprague Dawley Rats

Vascular tissues express heme oxygenase, which metabolizes heme to form carbon monoxide (CO). CO promotes relaxation of vascular smooth muscle but also inhibits nitric oxide (NO) formation. This study examines the hypothesis that CO promotes endothelium- and NO synthase-dependent vasoconstriction of isolated arterioles. Studies were conducted on pressurized first-order gracilis muscle arterioles isolated from anesthetized male Sprague-Dawley rats. Exogenous CO, as well as a heme precursor, δ-aminolevulinic acid (δ-ALA), constricted arterioles with intact endothelium pretreated with phenylephrine; these effects were abolished by removal of the endothelium. CO- and δ-ALA-induced vasoconstrictions were converted to dilations by pretreatment with an inhibitor of NO synthase, Nω-nitro-l-arginine methyl ester, or with Nω-nitro-l-arginine methyl ester and an NO donor, sodium nitroprusside. Furthermore, CO-induced vasoconstriction was prevented by pretreatment with the NO synthase substrate l-arginine. This study shows that exogenous, as well as endogenously formed, CO can promote endothelium-dependent vasoconstriction in isolated gracilis muscle arterioles. Because CO-induced vasoconstriction is abolished by NO synthase blockade and by l-arginine, CO most likely promotes endothelium-dependent vasoconstriction by inhibiting endothelial NO formation.

Nitric oxide and penile erection in streptozotocin-diabetic rats

1999 ◽  
Vol 96 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Gil ARI ◽  
Yoram VARDI ◽  
John P. M. FINBERG
Keyword(s):  
Methyl Ester ◽  
Time Course ◽  
Insulin Treatment ◽  
Diabetic Rats ◽  
No Synthase ◽  
Sprague Dawley ◽  
Nerve Roots ◽  
Sprague Dawley Rats ◽  
Pithed Rats ◽  
Stimulation Of

The purpose of this investigation was to study the time course, response to insulin and characteristics of erectile dysfunction in streptozotocin (STZ)-diabetic Sprague–Dawley rats, and the function of the NO-generating system in these animals. Copulation-induced and reflex erection were quantified in conscious Sprague–Dawley rats at different times after injection of STZ. The corporal vasodilatation response to nerve stimulation was studied by measuring the rise in corporal pressure in pithed rats following electrical stimulation of sacral spinal nerve roots. The activity of NO synthase was determined in corporal tissue by measuring the generation of [3H]citrulline from [3H]arginine. Copulation-induced erection was inhibited at 1 and 2 months after STZ treatment, but this could be prevented by a short (2-week) pretreatment with insulin. Reflex erection was inhibited at 1, 4, 6 and 9 months after STZ; at 6 months, this inhibition was also reversible by insulin pretreatment. Following pithing, the basal corporal pressure was elevated in diabetic rats. At 4 months after STZ, this increase was normalized by a 2-week, but not by a 1-week, pretreatment with insulin; however, at 9 months after STZ, insulin pretreatment did not normalize corporal pressure. The increase in corporal pressure caused by stimulation of sacral nerve roots in pithed rats was enhanced in diabetic animals. This enhancement was also normalized at 4 months, but not at 9 months, by 2 weeks of insulin treatment. The inhibition of the stimulation-induced increase in corporal pressure by NG-nitro-L-arginine methyl ester (5 mg/kg) was less following 9 months of diabetes, although NO synthase activity was normal in cavernosal tissue following 6–8 months of diabetes. In conclusion, STZ-induced diabetes caused changes in the erectile system that were initially reversible by a short insulin treatment, but which with time (more than 6 months) became irreversible. NO synthase activity in cavernosal tissue was normal, but the response to NG-nitro-L-arginine methyl ester was inhibited in long-term diabetes (9 months).

scholarly journals Heme Induction with Delta-Aminolevulinic Acid Stimulates an Increase in Water and Electrolyte Excretion

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Syed Quadri ◽  
Debra W. Jackson ◽  
Priyanka Prathipati ◽  
Courtney Dean ◽  
Keith E. Jackson
Keyword(s):  
Carbon Monoxide ◽  
Renal Function ◽  
Aminolevulinic Acid ◽  
Acute Administration ◽  
Bolus Administration ◽  
Sprague Dawley ◽  
Electrolyte Excretion ◽  
Sprague Dawley Rats ◽  
Before And After

Purpose. Studies were performed to examine hemodynamic and renal function before and after acute induction of the endogenous CO system with delta-aminolevulinic acid (DALA), which drives HO activity.Methods.In vivostudies were conducted on Inactin-anesthetized male Sprague Dawley rats (250–300 g) either with or without chronic pretreatment with L-NAME (50 mg/Kg, q12 hours x4d).Results. DALA (80 μmol/Kg, IV bolus) administration acutely increased endogenous CO production and HO-1 protein. In untreated and L-NAME-pretreated rats, DALA did not alter BP, GFR, or RBF but increased UF,UNaV, andUKV(untreated: Δ108.8 ± 0.28%, 172.1 ± 18.4%, and 165.2 ± 45.9%; pretreated: Δ109.4 ± 0.29%, 187.3 ± 26.9%, and 197.2 ± 45.7%). Acute administration of biliverdin (20 mg/kg, IV) and bilirubin (30 mg/kg, IV) to similarly treated animals did not alter UF,UNaV, andUKV.Conclusion. These results demonstrate that heme oxygenase induction increases urine and electrolyte excretion and suggest a direct tubular action of endogenous carbon monoxide.

Nω-Hydroxy-L-arginine and Its Homologues. Chemical and Biological Properties. A Review

2004 ◽  
Vol 69 (3) ◽  
pp. 499-510 ◽  
Author(s):  
Petra Beranová ◽  
Karel Chalupský ◽  
Gustav Entlicher
Keyword(s):  
Inhibitory Activity ◽  
Biological Activities ◽  
Biological Effects ◽  
Biological Properties ◽  
No Synthase ◽  
Point Of View ◽  
No Donor ◽  
Good Substrate ◽  
No Formation ◽  
Vasorelaxant Activity

Nω-Hydroxy-L-arginine (NOHA) is a stable intermediate in NO formation from L-arginine catalyzed by NO synthase (NOS). Apparently, NOHA can be released and serve as a stable reserve NO donor (as a substrate of NOS) or transported and exert its own biological effects. It shows endothelium-dependent as well as endothelium-independent vasorelaxant activity. The latter case indicates that NOHA can be metabolized by pathways independent of NOS. These possibilities are discussed in detail. Of the available NOHA homologues homo-NOHA is a good substrate of NOS while nor-NOHA seems to be a very poor substrate of this enzyme. On the contrary, nor-NOHA exerts arginase inhibitory activity 20 times higher than NOHA whereas homo-NOHA is inactive. Detailed investigation of biological activities of NOHA and its homologues seems to be promising from the pharmacological point of view. A review with 43 references.

Abstract P607: Nitric Oxide (NO) Regulates Paracellular Permselectivity in Isolated, Perfused Rat Thick Ascending Limbs through Claudin-19

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Casandra M Monzon ◽  
Jeffrey Garvin
Keyword(s):  
Nitric Oxide ◽  
Control Period ◽  
Sprague Dawley ◽  
Permeability Ratio ◽  
Ionic Selectivity ◽  
No Donor ◽  
Sprague Dawley Rats ◽  
Spermine Nonoate ◽  
Dilution Potential ◽  
Cl Permeability

About 50% of the Na reabsorbed in thick ascending limbs (TALs) traverses the paracellular pathway. The ionic selectivity of this route is regulated by claudins in the tight junctions. TALs express claudin-19 which has been reported to regulate TAL Na permeability. We showed that nitric oxide (NO) decreases Na/Cl permeability ratio (PNa/PCl) in TALs by increasing the absolute permeabilities of both ions though PCl increased more. However, whether NO affects paracellular permeability via claudin-19 is unknown. We hypothesize that NO regulates the paracellular permselectivity in TALs through this claudin. To test this we perfused TALs from Sprague Dawley rats and measured dilution potentials (a measure of permselectivity) with and without exogenously-added or endogenously-produced NO in the presence or absence of an antibody against an extracellular domain of claudin-19 or Tamm-Horsfall protein (control). Dilution potentials were generated by reducing bath NaCl from 141 to 32 mM. For the NO donor spermine NONOate (SPM): during the control period, the dilution potential was -9.3 ± 1.8 mV. After SPM (200 μM), it was -6.7 ± 1.6 mV (n = 6; p < 0.003). In the presence of the claudin-19 antibody, SPM had no significant effect on dilution potentials (claudin-19 antibody alone: -12.7 ± 2.1 mV vs claudin-19 antibody + SPM: -12.9 ± 2.4 mV; n = 6). The claudin-19 antibody alone had no effect on dilution potentials. In the presence of the Tamm-Horsfall protein, the effect of SPM was still present (Tamm-Horsfall protein antibody alone: -9.7 ± 1.0 mV; Tamm-Horsfall protein antibody + SPM: -6.3 ± 1.1 mV, p<0.006, n = 6). For experiments with endogenously-produced NO, L-arginine the substrate for NO synthase was added. During the control period, the dilution potential was -11.0 ± 1.1 mV. After L-arginine (500 μM) treatment, they were -9.0 ± 1.2 mV (n = 9; p < 0.05). In the presence of the claudin-19 antibody, L-arginine had no significant effect on dilution potentials (claudin-19 antibody alone: -10.1 ± 0.9 mV vs claudin-19 antibody + L-arginine: -10.1 ± 1.0 mV; n = 9). In the presence of the Tamm-Horsfall protein, the effect of L-arginine was still present. We conclude that the actions of NO on the paracellular permselectivity in thick ascending limbs are at least in part mediated by claudin-19.

scholarly journals Erythropoietin Produces a Dual Effect on Carotid Body Chemoreception in Male Rats

2021 ◽  
Vol 12 ◽  
Author(s):  
Christian Arias-Reyes ◽  
Sofien Laouafa ◽  
Natalia Zubieta-DeUrioste ◽  
Vincent Joseph ◽  
Aida Bairam ◽  
...  
Keyword(s):  
Carotid Body ◽  
No Synthase ◽  
Male Rats ◽  
High Dose ◽  
No Production ◽  
Sprague Dawley ◽  
En Bloc ◽  
No Synthase Inhibitor ◽  
Sprague Dawley Rats ◽  
Synthase Inhibitor

Erythropoietin (EPO) regulates respiration under conditions of normoxia and hypoxia through interaction with the respiratory centers of the brainstem. Here we investigate the dose-dependent impact of EPO in the CB response to hypoxia and hypercapnia. We show, in isolated “en bloc” carotid body (CB) preparations containing the carotid sinus nerve (CSN) from adult male Sprague Dawley rats, that EPO acts as a stimulator of CSN activity in response to hypoxia at concentrations below 0.5 IU/ml. Under hypercapnic conditions, EPO did not influence the CSN response. EPO concentrations above 0.5 IU/ml decreased the response of the CSN to both hypoxia and hypercapnia, reaching complete inhibition at 2 IU/ml. The inhibitory action of high-dose EPO on the CSN activity might result from an increase in nitric oxide (NO) production. Accordingly, CB preparations were incubated with 2 IU/ml EPO and the unspecific NO synthase inhibitor (L-NAME), or the neuronal-specific NO synthase inhibitor (7NI). Both NO inhibitors fully restored the CSN activity in response to hypoxia and hypercapnia in presence of EPO. Our results show that EPO activates the CB response to hypoxia when its concentration does not exceed the threshold at which NO inhibitors masks EPO’s action.

Abstract 93: Hypertension and Renal Injury Induced by Nitric Oxide Depletion are Ameliorated by Concomitant Depletion of Hydrogen Sulfide

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Sebastiaan Wesseling ◽  
Joost O Fledderus ◽  
Johanna A Dijk ◽  
Chantal Tilburgs ◽  
Marianne C Verhaar ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Renal Injury ◽  
Renal Damage ◽  
No Synthase ◽  
Tubular Epithelium ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Synthase Inhibitor

Chronic nitric oxide (NO) depletion induces hypertension and renal damage. Chronic kidney disease is associated with decreased NO availability and less renal H 2 S production. We hypothesized that combined depletion of NO and H 2 S aggravates hypertension and renal injury. Male 8-wk old Sprague Dawley rats were treated with vehicle, NO synthase inhibitor L-NG-nitroarginine (LNNA; 125 mg/L in drinking water), cystathionine-γ-lyase (CSE) inhibitor propargylglycine (PAG; 37.5 mg/kg BW ip daily) or LNNA + PAG for 1 and 4 weeks (6 rats/group). LNNA after 4w increased systolic blood pressure (SBP; 223±10 vs . 137±3 mmHg in controls; P<0.01), proteinuria (144±35 vs. 17±2 mg/d; P<0.01), uremia (16.6±4.2 vs . 7.0±0.4 mmol/L; P<0.05) and tubulo-interstitial injury (P<0.01). LNNA reduced urinary NO metabolite (NOx) excretion by ∼85% after 1w and 4w. PAG alone had no effect on SBP, renal function or injury, but did reduce urinary NOx excretion. Co-treatment with PAG ameliorated LNNA-induced hypertension (182±10 mmHg; P<0.01) and prevented proteinuria (27±3 mg/d), uremia (8.3±0.4 mmol/L) and tubulo-interstitial injury, but did not further reduce urinary NOx excretion. Renal H 2 S production was almost absent in all PAG groups after 1w and 4w (P<0.01) and was reduced in LNNA-treated rats after 4w (4.6±1.4 vs . 9.2±0.5 μmol/hr/mg; P<0.01). Renal HO-1 gene expression was strongly induced in all PAG-treated groups after 1w and 4w (4 to 19-fold; P<0.01) whereas LNNA only increased HO-1 gene expression at 4w (P<0.01). Immunohistochemistry showed that renal HO-1 protein was primarily interstitial in all PAG-treated groups at 1w and 4w. In contrast, LNNA only showed HO-1 in tubular epithelium in conjunction with protein casts. Depleting NO caused hypertension and renal damage followed by reduced renal H 2 S production and increased renal HO-1 expression. Surprisingly, concomitant inhibition of CSE ameliorated hypertension and prevented renal injury. PAG almost completely blocked renal H 2 S production and caused strong induction of renal HO-1, independently of injury, suggesting that H 2 S suppresses renal HO-1 expression. In conclusion, concomitant upregulation of HO-1 expression by inhibition of H 2 S production, prevents LNNA-induced hypertension and renal injury.

Mechanism underlying diuretic effect of l-NAME at a subpressor dose

2001 ◽  
Vol 281 (3) ◽  
pp. F414-F419 ◽  
Author(s):  
Mingyu Liang ◽  
Theresa J. Berndt ◽  
Franklyn G. Knox
Keyword(s):  
Proximal Tubule ◽  
Flow Rate ◽  
Nitrate Concentration ◽  
Distal Tubule ◽  
No Synthase ◽  
Urine Flow ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Renal Tubular ◽  
Nitrite Nitrate

The diuretic effects of nitric oxide (NO) synthase inhibitors administered at subpressor dose in rats are controversial, and the tubular segments involved are not known. In the present study, we examined the effect of N ω-nitro-l-arginine methyl ester (l-NAME) at a subpressor dose on renal interstitial NO and cGMP activity and on renal tubular segmental reabsorption of fluid in the rat. Intravenous infusion of l-NAME at 1 μg · kg−1 · min−1 in Sprague-Dawley rats ( N = 8), which did not alter mean arterial pressure or glomerular filtration rate, significantly increased urine flow rate (Uv; from 78.2 ± 12.7 to 117.1 ± 14.9 μl/min, P < 0.05). Paradoxically, this effect of l-NAME was concomitant with significant increases in nitrite/nitrate (from 10.79 ± 1.20 to 16.50 ± 2.60 μM, P < 0.05) and cGMP (from 0.65 ± 0.09 to 0.98 ± 0.18 nM, P < 0.05) concentrations in renal cortical microdialysate as well as the nitrite/nitrate concentration in the medullary microdialysate. Micropuncture studies in the superficial nephron revealed that l-NAME significantly increased the flow rate (from 8.3 ± 0.9 to 12.2 ± 1.2 nl/min, P < 0.05) and fractional delivery of fluid to the distal tubule, but not those in the late proximal tubule. In conclusion, l-NAME, at the subpressor dose used in this study, increased renal nitrate/nitrite and cGMP and inhibited fluid reabsorption in tubular segments between the late proximal tubule and the distal tubule of superficial nephrons.

17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage

2007 ◽  
Vol 292 (1) ◽  
pp. H245-H250 ◽  
Author(s):  
Zheng F. Ba ◽  
Ailing Lu ◽  
Tomoharu Shimizu ◽  
László Szalay ◽  
Martin G. Schwacha ◽  
...  
Keyword(s):  
Control Level ◽  
No Synthase ◽  
Sprague Dawley ◽  
Response Curves ◽  
Endothelin 1 ◽  
Sprague Dawley Rats ◽  
17Β Estradiol ◽  
Synthase Inhibitor

Although endothelin-1 (ET-1) induces vasoconstriction, it remains unknown whether 17β-estradiol (E2) treatment following trauma-hemorrhage alters these ET-1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor (ER) subtypes (ER-α and ER-β) and the endothelium-localized downstream mechanisms of actions of E2 remain unclear. We hypothesized that E2 attenuates increased ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma-hemorrhage with or without E2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET-1 were determined, and the vasoactive properties of E2, propylpyrazole triol (PPT, ER-α agonist), and diarylpropionitrile (DPN, ER-β agonist) were determined. The results showed that trauma-hemorrhage significantly increased ET-1-induced vasoconstriction; however, administration of E2 normalized ET-1-induced vasoconstriction in trauma-hemorrhage vessels to the sham-operated control level. The ER-β agonist DPN counteracted ET-1-induced vasoconstriction, whereas the ER-α agonist PPT was ineffective. Moreover, the vasorelaxing effects of E2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide (NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E2. Thus, E2 administration attenuates ET-1-induced vasoconstriction following trauma-hemorrhage via an ER-β-mediated pathway that is dependent on endothelium-derived NO synthesis.

Mechanisms of flow and ACh-induced dilation in rat soleus arterioles are altered by hindlimb unweighting

2002 ◽  
Vol 92 (3) ◽  
pp. 901-911 ◽  
Author(s):  
William G. Schrage ◽  
Christopher R. Woodman ◽  
M. Harold Laughlin
Keyword(s):  
Weight Bearing ◽  
Combined Treatment ◽  
Sprague Dawley ◽  
Hindlimb Unweighting ◽  
First Order ◽  
Sprague Dawley Rats ◽  
Independent Mechanism ◽  
Rat Soleus Muscle ◽  
Luminal Flow ◽  
Oxide Synthase

The purpose of this study was to test the hypothesis that endothelium-dependent dilation (flow-induced dilation and ACh-induced dilation) in rat soleus muscle arterioles is impaired by hindlimb unweighting (HLU). Male Sprague-Dawley rats (∼300 g) were exposed to HLU or weight-bearing control (Con) conditions for 14 days. Soleus first-order (1A) and second-order (2A) arterioles were isolated, cannulated, and exposed to step increases in luminal flow at constant pressure. Flow-induced dilation was not impaired by HLU in 1A or 2A arterioles. The cyclooxygenase inhibitor indomethacin (Indo; 50 μM) did not alter flow-induced dilation in 1As or 2As. Inhibition of nitric oxide synthase (NOS) with N ω-nitro-l-arginine (l-NNA; 300 μM) reduced flow-induced dilation by 65–70% in Con and HLU 1As. In contrast, l-NNA abolished flow-induced dilation in 2As from Con rats but had no effect in HLU 2As. Combined treatment with l-NNA + Indo reduced tone in 1As and 2As from Con rats, but flow-induced dilation in the presence of l-NNA + Indo was not different from responses without inhibitors in either Con or HLU 1As or 2As. HLU also did not impair ACh-induced dilation (10−9-10−4 M) in soleus 2As.l-NNA reduced ACh-induced dilation by ∼40% in Con 2As but abolished dilation in HLU 2As. Indo did not alter ACh-induced dilation in Con or HLU 2As, whereas combined treatment withl-NNA + Indo abolished ACh-induced dilation in 2As from both groups. We conclude that flow-induced dilation (1As and 2As) was preserved after 2 wk HLU, but HLU decreased the contribution of NOS in mediating flow-induced dilation and increased the contribution of a NOS- and cyclooxygenase-independent mechanism (possibly endothelium-derived hyperpolarizing factor). In soleus 2As, ACh-induced dilation was preserved after 2-wk HLU but the contribution of NOS in mediating ACh-induced dilation was increased.

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