scholarly journals Linolenic Acid Attenuates the Vasodilation Induced by Acetylcholine in Isolated Rat Aortae

Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989414 ◽  
Author(s):  
Soo Hee Lee ◽  
Seong-Ho Ok ◽  
Ji-Yoon Kim ◽  
Raghavendra Baregundi Subbarao ◽  
Sung Il Bae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Linolenic Acid ◽  
Calcium Ionophore ◽  
Underlying Mechanism ◽  
Cyclic Guanosine Monophosphate ◽  
Calcium Ionophore A23187 ◽  
Guanosine Monophosphate ◽  
Ionophore A23187 ◽  
Isolated Rat

This study aims to examine the effect of linolenic acid on the vasodilation or vasoconstriction induced by acetylcholine and bupivacaine in isolated rat aortae and its underlying mechanism. The effect of linolenic acid on the vasodilation induced by acetylcholine, the calcium ionophore A23187, sodium nitroprusside, and 8-bromoguanosine 3′,5′-cyclic monophosphate sodium salt (bromo-cyclic guanosine monophosphate [bromo-cGMP]) in endothelium-intact and endothelium-denuded aortae was examined. Linolenic acid inhibited vasodilation induced by acetylcholine, calcium ionophore A23187, and sodium nitroprusside. However, this fatty acid increased bromo-cGMP-induced vasodilation in endothelium-denuded aortae. Linolenic acid increased bupivacaine-induced contraction in endothelium-intact aortae, whereas it decreased bupivacaine-induced contraction in endothelium-intact aortae with Nω-nitro-l-arginine methyl ester and endothelium-denuded aortae. Linolenic acid inhibited acetylcholine- and bupivacaine-induced phosphorylation of endothelial nitric oxide synthase. Sodium nitroprusside increased cGMP in endothelium-denuded aortic strips, whereas bupivacaine decreased cGMP in endothelium-intact aortic strips. Linolenic acid decreased cGMP levels produced by bupivacaine and sodium nitroprusside. Together, these results suggest that linolenic acid inhibits acetylcholine-induced relaxation by inhibiting a step just prior to nitric oxide-induced cGMP formation. In addition, linolenic acid-mediated inhibition of vasodilation induced by a toxic concentration (3 × 10−4 M) of bupivacaine seems to be partially associated with inhibition of the nitric oxide–cGMP pathway.

scholarly journals Lipid Emulsion Attenuates Acetylcholine-Induced Relaxation in Isolated Rat Aorta

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Seong-Ho Ok ◽  
Soo Hee Lee ◽  
Jongsun Yu ◽  
Jungchul Park ◽  
Il-Woo Shin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Lipid Emulsion ◽  
Umbilical Vein ◽  
Calcium Ionophore ◽  
Rat Aorta ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Enos Phosphorylation ◽  
Isolated Rat

We investigated the effect of Lipofundin MCT/LCT and Intralipid on acetylcholine-induced nitric oxide- (NO-) mediated relaxation in rat aorta to determine which lipid emulsion (LE) is more potent in terms of inhibition of NO-induced relaxation. Dose-response curves of responses induced by acetylcholine, the calcium ionophore A23187, and sodium nitroprusside were generated using isolated rat aorta with or without LE. The effect of Lipofundin MCT/LCT on acetylcholine-induced endothelial nitric oxide synthase (eNOS) phosphorylation in human umbilical vein endothelial cells (HUVECs) was investigated using western blotting. Lipofundin MCT/LCT (0.1 and 0.2%) attenuated acetylcholine-induced relaxation in endothelium-intact aorta with or without tiron, whereas 0.2% Intralipid only inhibited relaxation. Lipofundin MCT/LCT inhibited relaxation induced by the calcium ionophore A23187 and sodium nitroprusside in endothelium-intact aorta, but Lipofundin MCT/LCT had no effect on sodium nitroprusside-induced relaxation in the endothelium-denuded aorta. Combined pretreatment withl-arginine plus Lipofundin MCT/LCT increased acetylcholine-induced maximal relaxation in endothelium-intact aorta compared with Lipofundin MCT/LCT alone.l-Arginine attenuated Lipofundin MCT/LCT-mediated inhibition of acetylcholine-induced eNOS phosphorylation in HUVECs. Taken together, Lipofundin MCT/LCT attenuated acetylcholine-induced NO-mediated relaxation via an inhibitory effect on the endothelium including eNOS, which is proximal to activation of guanylyl cyclase.

Sulfur dioxide induces vascular relaxation through PI3K/Akt/eNOS and NO/cGMP signaling pathways in rats

2020 ◽  
Vol 39 (8) ◽  
pp. 1108-1117
Author(s):  
Q Zhang ◽  
W Lyu ◽  
M Yu ◽  
Y Niu
Keyword(s):  
Nitric Oxide ◽  
Sulfur Dioxide ◽  
Signaling Pathways ◽  
Underlying Mechanism ◽  
Cyclic Guanosine Monophosphate ◽  
Rat Aorta ◽  
Guanosine Monophosphate ◽  
Signal Pathways ◽  
Atmospheric Pollutant ◽  
Protein Levels

Sulfur dioxide (SO2) is a common exogenous atmospheric pollutant. Studies have shown that SO2 can cause vasodilation as a gas signaling molecule, but the specific signaling pathways are not well understood. This study aimed to explore the underlying mechanism behind the effects of SO2 on vasodilation of isolated rat aorta. The results showed that when the dose of SO2 was 30 μM, the vasodilation of endothelium-intact rings was partially suppressed by LY294002 and NG-nitro-l-arginine methyl ester, and the protein levels of phosphoinositide 3-kinase (PI3K), p-Akt, and p-endothelial nitric oxide synthase ( p-eNOS) were significantly increased. When the dose of SO2 was 300 μM or 1500 μM, the vasodilation of endothelium-denuded rings did not change after application of the inhibitor, but the protein levels of PI3K, p-Akt, and p-eNOS were significantly decreased, and the activity of NOS and the level of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) were significantly increased. We speculate that the mechanism of SO2-induced vasodilatation likely involved the endothelial PI3K/Akt/eNOS and NO/cGMP signal pathways. In addition, at the concentration of 1500 μM, SO2 markedly increased the level of caspase-3 and caspase-9. The results suggest that high concentrations of SO2 may cause damage to blood vessels. This study will help to further inform the etiologies of SO2-related cardiovascular disease.

Segmental heterogeneity of NO-mediated pulmonary vasodilation in rats

1994 ◽  
Vol 267 (2) ◽  
pp. H494-H499 ◽  
Author(s):  
M. R. Eichinger ◽  
B. R. Walker
Keyword(s):  
Sodium Nitroprusside ◽  
Arginine Vasopressin ◽  
Calcium Ionophore ◽  
Vascular Occlusion ◽  
Physiological Saline ◽  
Calcium Ionophore A23187 ◽  
Pulmonary Vasculature ◽  
Ionophore A23187 ◽  
Sprague Dawley ◽  
No Donor

Nitric oxide (NO) is known to elicit vasodilation in the preconstricted rat lung. However, the sites of dilation within the pulmonary vasculature remain unknown. We hypothesized that donated NO would dilate all areas of constriction within the pulmonary vasculature, whereas receptor-mediated, NO-induced dilations would correspond to regional binding of agents. Isolated lungs from male Sprague-Dawley rats were perfused at constant flow with physiological saline solution. Pulmonary arterial and pulmonary venous pressures were monitored, while pulmonary microvascular pressures were estimated by vascular occlusion. Lungs were constricted with U-46619, and upon development of a stable degree of vasoconstriction, the NO donor sodium nitroprusside or the endothelium-dependent dilators A23187, arginine vasopressin, or ATP were administered. U-46619 caused constriction of both arterial and venous segments. Administration of sodium nitroprusside and the calcium ionophore A23187 elicited similar dilation of preconstricted arterial and venous segments. Arginine vasopressin significantly dilated both arterial and venous segments, with a greater reversal of venous resistance. In contrast, ATP significantly reduced arterial resistance more than venous. These results demonstrate that donated NO uniformly dilates all constricted regions of the pulmonary vasculature. However, receptor-mediated, endothelium-dependent dilators display characteristic heterogeneities in the sites of decreased pulmonary vascular resistance.

Endothelial modulation of porcine coronary microcirculation perfused via immature collaterals

1992 ◽  
Vol 262 (6) ◽  
pp. H1669-H1675 ◽  
Author(s):  
F. W. Sellke ◽  
Y. Kagaya ◽  
R. G. Johnson ◽  
T. Shafique ◽  
F. J. Schoen ◽  
...  
Keyword(s):  
Sodium Nitroprusside ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Flow State ◽  
Vascular Studies ◽  
Collateral Vessels ◽  
Endothelium Dependent Relaxation ◽  
Minimal Evidence ◽  
Dependent Agents

Porcine hearts have relatively few native collateral vessels and lack the propensity to develop normal perfusion to the collateral-dependent myocardium. To examine microvascular responses in the collateral-dependent region, collateral vessels were stimulated in pigs by the Ameroid constrictor technique. After 4–7 wk, isolated microarterial vessels (90–170 microns ID) were studied in a pressurized (40 mmHg), no-flow state. Microvessels from noninstrumented pigs were used as controls for vascular studies. Although myocardium in the collateral-dependent region showed minimal evidence of infarction, percent systolic shortening was reduced at rest and after pacing compared with myocardium in the normally perfused region. Relaxations to the receptor-mediated endothelium-dependent agents ADP and bradykinin were impaired in collateral-dependent coronary microvessels. Relaxations to the calcium ionophore A23187, which acts through a non-receptor-mediated mechanism, were similar in control and Ameroid microvessels. Relaxations to the endothelium-independent agent sodium nitroprusside were markedly enhanced in microvessels from the collateral-dependent region compared with microvessels from control hearts. In conclusion, receptor-mediated endothelium-dependent relaxation is impaired and endothelium-independent relaxation to sodium nitroprusside is enhanced in microvessels from myocardium perfused by immature collateral vessels.

scholarly journals Nitric oxide and peroxynitrite trigger and enhance release of neutrophil extracellular traps

2019 ◽  
Vol 77 (15) ◽  
pp. 3059-3075 ◽  
Author(s):  
Aneta Manda-Handzlik ◽  
Weronika Bystrzycka ◽  
Adrianna Cieloch ◽  
Eliza Glodkowska-Mrowka ◽  
Ewa Jankowska-Steifer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitrosative Stress ◽  
Calcium Ionophore ◽  
Neutrophil Extracellular Traps ◽  
Calcium Ionophore A23187 ◽  
Human Neutrophils ◽  
Ionophore A23187 ◽  
Inflammatory Reactions ◽  
Extracellular Traps

Abstract Despite great interest, the mechanism of neutrophil extracellular traps (NETs) release is not fully understood and some aspects of this process, e.g. the role of reactive nitrogen species (RNS), still remain unclear. Therefore, our aim was to investigate the mechanisms underlying RNS-induced formation of NETs and contribution of RNS to NETs release triggered by various physiological and synthetic stimuli. The involvement of RNS in NETs formation was studied in primary human neutrophils and differentiated human promyelocytic leukemia cells (HL-60 cells). RNS (peroxynitrite and nitric oxide) efficiently induced NETs release and potentiated NETs-inducing properties of platelet activating factor and lipopolysaccharide. RNS-induced NETs formation was independent of autophagy and histone citrullination, but dependent on the activity of phosphoinositide 3-kinases (PI3K) and myeloperoxidase, as well as selective degradation of histones H2A and H2B by neutrophil elastase. Additionally, NADPH oxidase activity was required to release NETs upon stimulation with NO, as shown in NADPH-deficient neutrophils isolated from patients with chronic granulomatous disease. The role of RNS was further supported by increased RNS synthesis upon stimulation of NETs release with phorbol 12-myristate 13-acetate and calcium ionophore A23187. Scavenging or inhibition of RNS formation diminished NETs release triggered by these stimuli while scavenging of peroxynitrite inhibited NO-induced NETs formation. Our data suggest that RNS may act as mediators and inducers of NETs release. These processes are PI3K-dependent and ROS-dependent. Since inflammatory reactions are often accompanied by nitrosative stress and NETs formation, our studies shed a new light on possible mechanisms engaged in various immune-mediated conditions.

Influence of vessel size on the sensitivity of porcine coronary microvessels to nitroglycerin

1990 ◽  
Vol 258 (2) ◽  
pp. H515-H520 ◽  
Author(s):  
F. W. Sellke ◽  
P. R. Myers ◽  
J. N. Bates ◽  
D. G. Harrison
Keyword(s):  
Nitric Oxide ◽  
Coronary Arteries ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Active Metabolites ◽  
Resistance Vessels ◽  
Relative Deficiency ◽  
Ly 83583

The responses of small (60–100 microns), medium (101–190 microns), and large (191–300 microns) porcine coronary microvessels to nitroglycerin were examined in vitro using a video-imaging apparatus. Large coronary microvessels, preconstricted with acetylcholine, relaxed by 90% in response to nitroglycerin, whereas small microvessels relaxed only 20% to nitroglycerin. Responses to putative metabolites of nitroglycerin, S-nitrosocysteine, and nitric oxide, were also examined. S-Nitrosocysteine produced equal relaxations in all sizes of coronary microvessels. Nitric oxide was 10 times more potent in large coronary arteries than in small but produced greater than 90% relaxation of all sizes of coronary microvessels at the highest concentrations. Bradykinin and the calcium ionophore A23187, which release endothelium-derived relaxing factor (EDRF), produced similar relaxation in small, medium, and large microvessels. The compound LY 83583 (which depletes vascular guanylate cyclase) reduced responses to nitroglycerin, nitric oxide, S-nitrosocysteine, bradykinin, and the calcium ionophore A23187 in microvessels of all sizes. Our data are compatible with the concept that nitroglycerin must undergo reductive processing to exert its vasodilator effect, likely through the formation of nitrosothiols. In small coronary microvessels, this biotransformation of nitroglycerin is diminished compared with larger coronary arteries. This may be caused by a relative deficiency of available sulfhydryl groups or a lack of enzymes necessary for conversion of nitroglycerin to its active metabolites in small coronary resistance vessels.

Effects of Halothane and Isoflurane on Carbon Monoxide-induced Relaxations in the Rat Aorta

1996 ◽  
Vol 85 (2) ◽  
pp. 347-354 ◽  
Author(s):  
Ming Jing ◽  
Saiid Bina ◽  
Ajay Verma ◽  
Jayne L. Hart ◽  
Sheila M. Muldoon
Keyword(s):  
Nitric Oxide ◽  
Carbon Monoxide ◽  
Cyclic Guanosine Monophosphate ◽  
Rat Aorta ◽  
Isometric Tension ◽  
Guanosine Monophosphate ◽  
Second Procedure ◽  
Dose Dependent ◽  
Cgmp Formation ◽  
Isolated Rat

Background Halothane and isoflurane previously were reported to attenuate endothelium-derived relaxing factor/nitric oxide-mediated vasodilation and cyclic guanosine monophosphate (cGMP) formation in isolated rat aortic rings. Carbon monoxide has many chemical and physiologic similarities to nitric oxide. This study was designed to investigate the effects of halothane and isoflurane on carbon monoxide-induced relaxations and cGMP formation in the isolated rat aorta. Methods Isometric tension was recorded continuously from endothelium denuded rat aortic rings suspended in Krebs-filled organ baths. Rings precontracted with submaximal concentrations of norepinephrine were exposed to cumulative concentrations of carbon monoxide (26-176 microM). This procedure was repeated three times, with anesthetics delivered 10 min before the second procedure. Carbon monoxide responses of rings contracted with the same concentration of norepinephrine (10(-6) M and 2 x 10(-6) M) used in the anesthetic-exposed preparations also were examined. The concentrations of cGMP were determined in denuded rings using radioimmunoassay. The rings were treated with carbon monoxide (176 microM, 30 s) alone, or carbon monoxide after a 10-min incubation with halothane (0.34 mM or 0.72 mM). To determine whether the sequence of anesthetic delivery influenced results, vascular rings pretreated with halothane were compared with nonpretreated rings. Results Carbon monoxide (26-176 microM) caused a dose-dependent reduction of norepinephrine-induced tension, with a maximal relaxation of 1.51 +/- 0.07 g (85 +/- 7% of norepinephrine-induced contraction). Halothane (0.34 mM and 0.72 mM) significantly attenuated the carbon monoxide-induced relaxations, but only the highest concentration of isoflurane (0.53 mM) significantly attenuated the carbon monoxide-induced relaxations. Carbon monoxide (176 microM) significantly increased cGMP content (+88.1 +/- 7.1%) and preincubation of the aortic rings with halothane (0.34 mM and 0.72 mM) inhibited this increase (-70.7 +/- 6.8% and -108.1 +/- 10.6%, respectively). When aortic rings and carbon monoxide were added simultaneously to Krebs solution equilibrated with halothane (0.72 mM), no inhibition of cGMP formation occurred. Conclusion Carbon monoxide-induced endothelium-independent relaxations of rat aortic rings were decreased by clinically relevant concentrations of halothane and isoflurane. The carbon monoxide-induced elevations of cGMP were attenuated by halothane only when the anesthetic was incubated with aortic rings before carbon monoxide treatment. The possible clinical significance of the actions of the anesthetics on this endogenous vasodilator is yet to be determined.

Selective production of endothelium-derived nitric oxide in canine femoral veins

1991 ◽  
Vol 261 (3) ◽  
pp. H677-H682 ◽  
Author(s):  
V. M. Miller
Keyword(s):  
Nitric Oxide ◽  
Isometric Force ◽  
Calcium Ionophore ◽  
Calcium Ionophore A23187 ◽  
Ionophore A23187 ◽  
Adrenergic Agonist ◽  
Thrombin Receptors ◽  
Systemic Vein ◽  
The Difference ◽  
Arteries And Veins

In arteries, analogues of L-arginine inhibit the synthesis of nitric oxide and thereby reduce endothelium-dependent relaxations. Experiments were designed to determine whether analogues of L-arginine affect endothelium-dependent responses in a systemic vein. Rings cut from canine femoral arteries and veins were suspended for the measurement of isometric force in organ chambers. In some rings, the endothelium was deliberately removed. All experiments were conducted in the presence of indomethacin (10(-5) M). NG-monomethyl-L-arginine (L-NMMA, 10(-4) M) reduced significantly endothelium-dependent relaxations to acetylcholine, ADP, and thrombin in arteries but not in veins. In the veins, the alpha 2-adrenergic agonist BHT-920 caused contractions which were reduced in rings with endothelium. L-NMMA eliminated the difference in contraction between rings with and without endothelium in the veins. This effect was reversed by L- but not D-arginine (3 x 10(-4) M). N omega-nitro-L-arginine (10(-4) M) reduced endothelium-dependent relaxations to acetylcholine, thrombin, and the calcium ionophore A23187 in venous rings. However, it did not alter the contractions to BHT-920 in rings with or without endothelium. L-Canavanine did not alter endothelium-dependent relaxations in the veins. These results suggest that synthesis of nitric oxide is associated with stimulation of alpha 2-adrenergic, muscarinic, and thrombin receptors on venous endothelial cells. Furthermore, the analogues of L-arginine affect endothelium-dependent relaxations in canine veins differentially.

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