Effect of fatty acids on endothelium-dependent relaxation in the rabbit aorta

2006 ◽  
Vol 111 (2) ◽  
pp. 145-151 ◽  
Author(s):  
Indika Edirisinghe ◽  
Kellie McCormick Hallam ◽  
C. Tissa Kappagoda
Keyword(s):  
Nitric Oxide ◽  
Fatty Acids ◽  
Stearic Acid ◽  
Time Course ◽  
Plasma Concentrations ◽  
Rabbit Aorta ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
The Metabolic Syndrome ◽  
Endothelium Dependent Relaxation

The metabolic syndrome, Type II (non-insulin-dependent) diabetes and obesity are associated with endothelial dysfunction and increased plasma concentrations of NEFAs (non-esterified fatty acids; free fatty acids). The present study was undertaken to define the inhibitory effects of saturated NEFAs on EDR (endothelium-dependent relaxation). Experiments were performed in rings of rabbit aorta to establish (i) dose–response relationships, (ii) the effect of chain length, (iii) the effect of the presence of double bonds, (iv) reversibility and time course of inhibition, and (v) the effect on nitric oxide production. Aortic rings were incubated (1 h) with NEFA–albumin complexes derived from lauric (C12:0), myristic (C14:0), palmitic (C16:0), stearic (C18:0) and linolenic (C18:3) acids. EDR induced by acetylcholine (0.1–10 μmol/l) was measured after pre-contraction with noradrenaline. Inhibition of EDR was dose-dependent (0.5–2 mmol/l NEFA), and the greatest inhibition (51%) was observed with stearic acid (2 mmol/l). Lauric acid had the smallest inhibitory effect. The inhibitory effects were always reversible and were evident after 15 min of incubation. Linolenic acid caused a significantly lower inhibition of EDR than stearic acid. SOD (superoxide dismutase) restored the inhibitory effect caused by NEFAs, suggesting the involvement of ROS (reactive oxygen species) in removing nitric oxide. The nitric oxide concentration measured after exposure of the rings to acetylcholine was lower after incubation with NEFAs than with Krebs buffer alone. This finding is consistent with removal of nitric oxide by ROS. This claim was supported by the demonstration of increased concentrations of nitrated tyrosine in the rings incubated with NEFAs.

scholarly journals Effect of fatty acid chain length and saturation on the gastrointestinal handling and metabolic disposal of dietary fatty acids in women

1999 ◽  
Vol 81 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Amanda E. Jones ◽  
Michael Stolinski ◽  
Ruth D. Smith ◽  
Jane L. Murphy ◽  
Stephen A. Wootton
Keyword(s):  
Fatty Acids ◽  
Oleic Acid ◽  
Stearic Acid ◽  
Palmitic Acid ◽  
Chain Length ◽  
Time Course ◽  
Absorbed Dose ◽  
Dietary Fatty Acids ◽  
Fatty Acid Chain ◽  
Degree Of Unsaturation

The gastrointestinal handling and metabolic disposal of [1-13C]palmitic acid, [1-13C]stearic acid and [1-13C]oleic acid administered within a lipid–casein–glucose–sucrose emulsion were examined in normal healthy women by determining both the amount and nature of the13C label in stool and label excreted on breath as13CO2. The greatest excretion of13C label in stool was in the stearic acid trial (9.2 % of administered dose) whilst comparatively little label was observed in stool in either the palmitic acid (1.2 % of administered dose) or oleic acid (1.9 % of administered dose) trials. In both the palmitic acid and oleic acid trials, all of the label in stool was identified as being present in the form in which it was administered (i.e. [13C]palmitic acid in the palmitic acid trial and [13C]oleic acid in the oleic acid trial). In contrast, only 87 % of the label in the stool in the stearic acid trial was identified as [13C]stearic acid, the remainder was identified as [13C]palmitic acid which may reflect chain shortening of [1-13C]stearic acid within the gastrointestinal tract. Small, but statistically significant, differences were observed in the time course of recovery of13C label on breath over the initial 9 h of the study period (oleic acid = palmitic acid > stearic acid). However, when calculated over the 24 h study period, the recovery of the label as13CO2was similar in all three trials (approximately 25 % of absorbed dose). These results support the view that chain length and degree of unsaturation may influence the gastrointestinal handling and immediate metabolic disposal of these fatty acids even when presented within an emulsion.

scholarly journals Regulation of nitric oxide synthase isoforms and role of nitric oxide during prostaglandin F2alpha-induced luteolysis in rabbits

Reproduction ◽  
2003 ◽  
pp. 807-816 ◽  
Author(s):  
C Boiti ◽  
G Guelfi ◽  
D Zampini ◽  
G Brecchia ◽  
A Gobbetti ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Time Course ◽  
Plasma Concentrations ◽  
Physiological Role ◽  
Total Activity ◽  
Corpora Lutea ◽  
Prostaglandin F ◽  
Oxide Synthase

Total activity of nitric oxide synthase (NOS) and the gene expression of both endothelial NOS (eNOS) and inducible NOS (iNOS) isoforms in corpora lutea of pseudopregnant rabbits were examined during prostaglandin F(2alpha) (PGF(2alpha))-induced luteolysis. Corpora lutea were collected at 0, 6, 12, 24 and 48 h after an injection of PGF(2alpha) at day 9 of pseudopregnancy. At 12 h after PGF(2alpha) administration, luteal mRNA encoding eNOS decreased (P0.05) by 40% and remained low throughout the subsequent 36 h, whereas eNOS protein increased (P0.05) two- to threefold. By contrast, expression of mRNA encoding iNOS was poor and remained fairly constant, but transcription increased eightfold (P0.01) within 6 h after PGF(2alpha) treatment and then decreased to values similar to those of controls. Total NOS activity increased twofold (P0.01) at 6 h after treatment and remained high thereafter, whereas progesterone concentrations in explanted corpora lutea decreased (P0.01) from 302.4+/-42.3 pg x mg(-1) at day 9 to 58.6+/-8.3 at 48 h later, and peripheral plasma concentrations of progesterone declined too. Long-term administration of Nomega-nitro-L-arginine methyl ester (0.6 g l(-1) per os) from day 2 of pseudopregnancy onward partially blocked the luteolytic action of PGF(2alpha) administered at day 9 of pseudopregnancy. In nitric oxide (NO)-deficient rabbits, progesterone concentrations remained higher (P0.01) than in controls at 24-48 h after PGF(2alpha) administration (4.5 to 3.2 ng x ml(-1), respectively). These data are the first to characterize NOS activity. The time course of expression of eNOS and iNOS in rabbit corpora lutea during PGF(2alpha)-induced luteolysis gives additional support to a physiological role of NO in the regulation of regression of corpora lutea in rabbits.

scholarly journals Inhibitory effects of polyunsaturated fatty acids on Kv4/KChIP potassium channels

2009 ◽  
Vol 296 (5) ◽  
pp. C1003-C1014 ◽  
Author(s):  
Linda M. Boland ◽  
Michelle M. Drzewiecki ◽  
Gabriela Timoney ◽  
Erin Casey
Keyword(s):  
Fatty Acids ◽  
Potassium Channels ◽  
Polyunsaturated Fatty Acids ◽  
Time Course ◽  
Expression System ◽  
K Channel ◽  
Xenopus Laevis Oocyte ◽  
Inhibitory Effects ◽  
Interacting Protein ◽  
Steady State Inactivation

Kv4/K channel interacting protein (KChIP) potassium channels are a major class of rapidly inactivating K+ channels in neurons and cardiac muscle. Modulation of Kv4/KChIP channels by polyunsaturated fatty acids (PUFAs) is important in the regulation of cellular excitability and the induction of activity-dependent synaptic plasticity. Using the Xenopus laevis oocyte expression system, we studied the inhibition by PUFAs of the peak outward K+ current and the accompanying increase in the rate of current inactivation of rKv4.2/rKChIP1b. Inhibitory effects do not depend on KChIP coexpression since Kv4.2 channels lacking an NH2-terminal KChIP association region were substantially inhibited by PUFAs and showed strong kinetic modulation. PUFAs accelerated both the fast and slow time constants that describe the kinetics of Kv4/KChIP inactivation. The time course of entry into closed inactivated states was facilitated by PUFAs, but steady-state inactivation and recovery from inactivation were unaltered. PUFA inhibition of Kv4/KChIP current was not use dependent. The concentration-response relationship for arachidonic acid (AA) inhibition of Kv4/KChIP channels mimicked that for activation of TRAAK channels. Internal serum albumin largely prevents the inhibitory effects of externally applied AA, and the membrane-impermeant AA-CoA is inactive when applied externally. Overall, our data suggest that PUFAs inhibit Kv4/KChIP channels by facilitating inactivation from open and closed gating states and that access of the fatty acid to the internal leaflet of the membrane is important. These results improve our understanding of the mechanisms for the inhibitory effects of PUFAs on Kv4/KChIP channel function.

The association of N ε-Carboxymethyllysine with polyunsaturated and saturated fatty acids in healthy individuals

2021 ◽  
Author(s):  
Permal Deo ◽  
Varinderpal S Dhillon ◽  
Philip Thomas ◽  
Michael Fenech
Keyword(s):  
Fatty Acids ◽  
Regression Analysis ◽  
Stearic Acid ◽  
Saturated Fatty Acids ◽  
Plasma Concentrations ◽  
Positive Association ◽  
Docosapentaenoic Acid ◽  
Healthy Individuals ◽  
Strong Negative Correlation ◽  
And Gender

Abstract Red blood cell (RBC) fatty acids status is used as a biomarker of dietary intake of fats however, there is still a paucity of evidence regarding individual fatty acids and modulation of endogenous advanced glycation end-product (AGE) levels. Due to membrane PUFA being a well-known target for peroxidation, we hypothesized that cellular PUFAs are positively associated with circulatory N ε-carboxymethyllysine (CML) that is also influenced by glyoxal (GO) levels in healthy cohorts. To test this, we investigated the association between RBC fatty acids and circulatory AGEs biomarkers in healthy individuals. The results showed a negative association between saturated fatty acids (SFA) and CML and stepwise multivariate regression analysis indicated stearic acid was negatively associated with CML levels (β = -0.200, p=0.008) after adjusting for age, BMI, and gender. In addition, stearic acid: palmitic acid ratio was also negatively correlated with plasma concentrations of CML (rp= -0.191, p = 0.012) and glucose (rp= -0.288, p = 0.0001). Polyunsaturated fatty acids (PUFA) showed a positive association with CML levels particularly, docosapentaenoic acid, γ-Linolenic acid, arachidonic acid, and docosadienoic acid. However, these associations were not evident after the multiple regression analysis adjusted for age, BMI, and gender. A strong negative correlation (rp= -0.98, p< 0.0001) between total PUFA and total SFA was observed. Furthermore, the SFA:PUFA ratio was inversely correlated with CML (rp= -0.227, p< 0.003). Overall, this study indicates that different fats and their combinations may influence the formation of AGEs and that carefully controlled interventions are required to further test this hypothesis.

scholarly journals Endothelium-dependent responses in human isolated thyroid arteries from donors

2004 ◽  
Vol 181 (3) ◽  
pp. 379-384 ◽  
Author(s):  
B Torondel ◽  
JM Vila ◽  
G Segarra ◽  
P Lluch ◽  
P Medina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dominant Role ◽  
Human Thyroid ◽  
K Channel ◽  
Organ Donors ◽  
Inhibitory Effects ◽  
K Channels ◽  
High K ◽  
Inwardly Rectifying ◽  
Endothelium Dependent Relaxation

The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect was not modified by indomethacin and was only partly reduced by L-NMMA, but was abolished in endothelium-denuded rings. The relaxation resistant to indomethacin and L-NMMA was abolished by using either apamin combined with charybdotoxin, ouabain plus barium, or a high-K(+) solution. Noradrenaline induced concentration-dependent contractions which were of greater magnitude in arteries denuded of endothelium or in the presence of L-NMMA.In conclusion, the results indicate that in human thyroid arteries the endothelium significantly modulates responses to acetylcholine and noradrenaline through the release of NO and EDHF. EDHF plays a dominant role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels and Na(+)-K(+)-ATPase.

scholarly journals Involvement of nitric oxide in the endothelium-dependent relaxation induced by hydrogen peroxide in the rabbit aorta

1993 ◽  
Vol 110 (1) ◽  
pp. 151-158 ◽  
Author(s):  
Artur Zembowicz ◽  
Richard J. Hatchett ◽  
Andrzej M. Jakubowski ◽  
Richard J. Gryglewski
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Peroxide ◽  
Rabbit Aorta ◽  
Endothelium Dependent Relaxation

Effect of nitric oxide synthase inhibitors on endothelial [Ca2+]i and microvessel permeability

1997 ◽  
Vol 272 (1) ◽  
pp. H176-H185 ◽  
Author(s):  
P. He ◽  
B. Liu ◽  
F. E. Curry
Keyword(s):  
Nitric Oxide ◽  
Time Course ◽  
Calcium Ionophore ◽  
Inhibitory Effect ◽  
Initial Increase ◽  
Calcium Dependent ◽  
Nos Inhibitors ◽  
Before And After ◽  
Microvessel Permeability

To investigate the mechanism whereby nitric oxide (NO) signaling pathways regulate microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic calcium concentration ([Ca2+]i) in response to calcium ionophore, ionomycin (5 microM), and ATP (10 microM) before and after the use of NO synthase (NOS) inhibitors in single perfused frog mesenteric venular microvessels. Ionomycin induced a transient increase in endothelial [Ca2+]i and an associated increase in Lp. The NOS inhibitors N omega-nitro-L-arginine methyl ester (10 and 300 microM) and N omega-monomethyl-L-arginine (L-NMMA; 10, 50, and 100 microM) significantly attenuated the peak increase in Lp induced by ionomycin. A similar inhibitory effect was also observed with the increase in Lp mediated by ATP. In contrast, D-NMMA, a biologically inactive isomer of L-NMMA, showed no effect on ionomycin-induced increase in Lp L-Arginine (3 mM) reversed the inhibitory effect of L-NMMA (10 microM) on Lp. However, the NOS inhibitors did not alter the magnitude and time course of the biphasic increase in endothelial [Ca2+]i induced by both ionomycin and ATP. These data suggest that 1) calcium-dependent NO release is a necessary step to increase microvessel permeability, and 2) the action of NOS inhibitors in attenuating the permeability increase in response to ionomycin and ATP occurs down-stream from calcium entry and does not involve modification of the initial increase in endothelial [Ca2+]i.

Thiopental inhibits nitric oxide production in rat aorta

1999 ◽  
Vol 77 (12) ◽  
pp. 958-966 ◽  
Author(s):  
Carlos Castillo ◽  
Juan Asbun ◽  
Bruno Escalante ◽  
Carlos M Villalón ◽  
Pedro López ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Rat Aorta ◽  
Nitric Oxide Production ◽  
Nitric Oxide Synthesis ◽  
Oxide Production ◽  
Nitrite Production ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Endothelium Dependent Relaxation

We studied whether thiopental affects endothelial nitric oxide dependent vasodilator responses and nitrite production (an indicator of nitric oxide production) elicited by acetylcholine, histamine, and A23187 in rat aorta (artery in which nitric oxide is the main endothelial relaxant factor). In addition, we evaluated the barbiturate effect on nitric oxide synthase (NOS) activity in both rat aorta and kidney homogenates. Thiopental (10-100 µg/mL) reversibly inhibited the endothelium-dependent relaxation elicited by acetylcholine, histamine, and A23187. On the contrary, this anesthetic did not modify the endothelium-independent but cGMP-dependent relaxation elicited by sodium nitroprusside (1 nM - 1 µM) and nitroglycerin (1 nM - 1 µM), thus excluding an effect of thiopental on guanylate cyclase of vascular smooth muscle. Thiopental (100 µg/mL) inhibited both basal (87.8 ± 14.3%) and acetylcholine- or A23187-stimulated (78.6 ± 3.9 and 39.7 ± 5.6%, respectively) production of nitrites in aortic rings. In addition the barbiturate inhibited (100 µg/mL) the NOS (45 ± 4 and 42.8 ± 9%) in aortic and kidney homogenates, respectively (measured as 14C-labeled citrulline production). In conclusion, thiopental inhibition of endothelium-dependent relaxation and nitrite production in aortic rings strongly suggests an inhibitory effect on NOS. Thiopental inhibition of the NOS provides further support to this contention.Key words: thiopental, rat aorta, endothelium-dependent relaxation, nitric oxide synthesis.

Differential effect of difluoromethylornithine on the increases in plasma concentrations of reproductive hormones on the afternoon of pro-oestrus in the rat

1989 ◽  
Vol 121 (3) ◽  
pp. 495-499 ◽  
Author(s):  
S. A. Nicholson ◽  
G. A. Wynne-Jones
Keyword(s):  
Differential Effect ◽  
Time Course ◽  
Plasma Concentrations ◽  
Specific Inhibitor ◽  
Inhibitory Effect ◽  
Prolactin Secretion ◽  
Reproductive Hormones ◽  
Female Rats ◽  
Limited Time ◽  
The Times

ABSTRACT In our colony of female rats (220–320 g body weight) undergoing regular 4-day oestrous cycles there were significant, marked rises in concentrations of LH, FSH and prolactin between 09.00 and 19.00 h on pro-oestrus. The i.p. injection of difluoromethylornithine (DFMO; 40–400 mg/kg), a specific inhibitor of the activity of ornithine decarboxylase, at 15.00 h on prooestrus had a differential effect on the rise in plasma concentrations of the various hormones thereafter. The drug produced a significant, partial, dose-related suppression of the rise in plasma concentrations of LH and prolactin, but had no significant effect on the rise in FSH. For time-course studies, 120 mg DFMO/kg were injected at 13.00, 15.00 or 17.00 h and groups of animals killed at 19.00 h. Only the injection at 15.00 h was effective in causing a significant reduction in plasma concentrations of LH and prolactin at 19.00 h. Pituitary content of the hormones was found to be unaffected by the administration of DFMO at the times and doses tested. These results suggest that DFMO has a selective inhibitory effect on enhanced LH and prolactin secretion on the afternoon of pro-oestrus in the rat, whilst not affecting FSH release. There seems to be a limited time (after 13.00 but before 17.00 h) during which its administration is effective. Journal of Endocrinology (1989) 121, 495–499

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