Effect of NG-Monomethyl-l-Arginine on Endothelium-Dependent Relaxation of Human Subcutaneous Resistance Arteries

1990 ◽  
Vol 79 (3) ◽  
pp. 273-278 ◽  
Author(s):  
Robin G. Woolfson ◽  
Lucilla Poston
Keyword(s):  
Inhibitory Action ◽  
Contractile Response ◽  
Physiological Saline ◽  
Isometric Tension ◽  
The Novel ◽  
Resistance Arteries ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation ◽  
Stimulation Of

1. Using a myograph to measure isometric tension, we have looked at the action of NG-monomethyl-l-arginine on the endothelium-dependent relaxation of human subcutaneous resistance arteries. 2. NG-Monomethyl-l-arginine, the novel inhibitor of endothelium-derived relaxing factor synthesis, caused concentration-dependent but only partial inhibition of maximal relaxation induced by acetylcholine in human subcutaneous resistance arteries. 3. The inhibitory action of NG-monomethyl-l-arginine on acetylcholine-induced maximal relaxation was partially reversed by incubation of the arteries in equimolar concentrations of l-arginine and NG-monomethyl-l-arginine. Subsequent incubation in l-arginine led to further reversal, but this was no greater than with incubation in physiological saline. 4. A component of acetylcholine-induced relaxation was sensitive to indomethacin, suggesting that this response is mediated by prostanoids as well as by endothelium-derived relaxing factor. 5. NG-Monomethyl-l-arginine did not increase the tension of resting human subcutaneous resistance arteries. NG-Monomethyl-l-arginine did enhance the contractile response to noradrenaline, possibly due to inhibition of release of endothelium-derived relaxing factor resulting from stimulation of α2-adrenoreceptors on the endothelial cells.

Endothelium-derived contracting and relaxing factors contribute to hypoxic responses of pulmonary arteries

1993 ◽  
Vol 265 (4) ◽  
pp. H1139-H1148 ◽  
Author(s):  
K. L. Kovitz ◽  
T. D. Aleskowitch ◽  
J. T. Sylvester ◽  
N. A. Flavahan
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Arteries ◽  
Initial Response ◽  
Isometric Tension ◽  
No Synthase ◽  
Moderate Hypoxia ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Increased Activity ◽  
Endothelium Dependent Relaxation

The response of porcine pulmonary arteries to hypoxia depended on their location in the vasculature and the degree and duration of the hypoxic challenge. In rings of pulmonary artery suspended for isometric tension recording (37 degrees C, 16% O2 and 5% CO2), moderate hypoxia (10% and 4% O2) caused endothelium-dependent relaxation in distal arteries but transient endothelium-dependent contraction in proximal arteries. In both proximal and distal arteries, the initial response to anoxia (0% O2) was a transient endothelium-dependent contraction. This was followed by a slowly developing, sustained endothelium-dependent contraction in proximal arteries, or by an endothelium-independent relaxation in distal arteries. The endothelium-dependent relaxation to moderate hypoxia in distal arteries was inhibited only by combined inhibition of endothelium-derived relaxing factor (EDRF)-nitric oxide (NO) synthase [N omega-nitro-L-arginine methyl ester (L-NAME)] and cyclooxygenase (indomethacin), suggesting mediation by EDRF-NO and prostacyclin. Transient endothelium-dependent contractions to moderate hypoxia (proximal arteries) or anoxia (all arteries) were abolished by L-NAME, but the late endothelium-dependent anoxic contraction observed in proximal arteries was not reduced by L-NAME and/or indomethacin. Therefore, hypoxia/anoxia may initiate contraction of pulmonary arteries by decreasing the activity of EDRF-NO, but the contractions appear to be maintained by an increased activity of an endothelium-derived contracting factor.

Effects of hypoxia on endothelium-dependent relaxation of rat pulmonary artery

1990 ◽  
Vol 258 (4) ◽  
pp. L207-L214 ◽  
Author(s):  
D. M. Rodman ◽  
T. Yamaguchi ◽  
K. Hasunuma ◽  
R. F. O'Brien ◽  
I. F. McMurtry
Keyword(s):  
Pulmonary Artery ◽  
Branch Pulmonary Artery ◽  
Cyclic Monophosphate ◽  
Relaxing Factor ◽  
Chemical Inhibitors ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation ◽  
Isolated Rat ◽  
Stimulation Of ◽  
Do So

We have previously reported that the isolated rat branch pulmonary artery (PA) contracts when made hypoxic and that the contraction is dependent in large part on the presence of a functioning endothelium. This study tested if the hypoxic contraction was caused by reduced endothelium-derived relaxing factor (EDRF) activity. To do so we tested if chemical inhibitors of EDRF mimicked the effect of hypoxia, if PA guanosine 3',5'-cyclic monophosphate (cGMP) fell during hypoxic contraction, and if stimulation of smooth muscle cGMP attenuated hypoxic contraction. We found that the EDRF inhibitors hemoglobin and methylene blue caused a concentration-dependent increase in PA force that equaled that produced by hypoxia. PA cGMP decreased in endothelium-intact rings from 105 +/- 14 pM/g (wet wt) during normoxia to 41 +/- 9 pM/g during hypoxia. In endothelium-denuded rings normoxic cGMP was reduced to 32 +/- 10 pM/g with no further decrease during hypoxia. The endothelium-independent stimulators of cGMP, nitric oxide, and 8-bromo-cGMP, reduced maximum hypoxic contraction by 80 +/- 11 and 93 +/- 3%, respectively, whereas the endothelium-dependent stimulator acetylcholine did not. PA adenosine 3',5'-cyclic monophosphate (cAMP) fell only slightly during hypoxia and cAMP inhibitors failed to mimic the hypoxic contraction. We conclude that the hypoxic contraction of isolated rat PA is caused largely by decreased EDRF activity.

Endothelial modulation of renal interlobar arteries from pregnant rats

1993 ◽  
Vol 265 (2) ◽  
pp. F309-F315
Author(s):  
K. C. Griggs ◽  
K. P. Conrad ◽  
K. Mackey ◽  
M. K. McLaughlin
Keyword(s):  
Late Gestation ◽  
Resistance Arteries ◽  
Renal Vasculature ◽  
Pregnant Rats ◽  
Relaxing Factor ◽  
Increased Sensitivity ◽  
Endothelium Derived Relaxing Factor ◽  
Oxide Synthase ◽  
Endothelium Dependent Relaxation ◽  
Group Concentration

The purpose of this study was to determine whether there are gestational effects on 1) the response of resistance arteries from the renal vasculature to phenylephrine and 2) the endothelial modulation of these arteries. Interlobar arteries (200-300 microns ID) were isolated from the kidneys of virgin and pregnant rats at 18-20 days of gestation (term, 22 +/- 1 days) and studied in a pressurized arteriograph system. Intact arteries from virgin and pregnant rats did not differ in sensitivity to phenylephrine. Arteries without endothelium from both groups were more sensitive to phenylephrine than arteries with endothelium. Sensitivity was increased 3.4-fold by endothelial removal in arteries from virgin rats and 1.5-fold in the pregnant group. Concentration-response relationships to phenylephrine were determined in arteries with endothelium and then repeated in the presence of 2.5 x 10(-4) M N omega-nitro-L-arginine (L-NNA), an inhibitor of nitric oxide synthase. All arteries were more sensitive to phenylephrine in the presence of L-NNA, with an average increase of 3.2-fold for the arteries from virgin rats and 1.6-fold from pregnant rats. These results indicate that the increased sensitivity to phenylephrine is primarily due to elimination of endothelium-derived relaxing factor (EDRF) and that basal EDRF activity is decreased during late gestation. To determine whether stimulated endothelium-dependent relaxation is enhanced in pregnancy, arteries with endothelium were constricted with phenylephrine to 50% of their maximum and relaxed to increasing concentrations of methacholine.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of atherosclerosis on endothelium-dependent relaxation in the aorta and intracranial arteries of rabbits

1989 ◽  
Vol 70 (5) ◽  
pp. 793-798 ◽  
Author(s):  
Kenji Kanamaru ◽  
Shiro Waga ◽  
Hiroshi Tochio ◽  
Kazuhiko Nagatani
Keyword(s):  
Carotid Arteries ◽  
Isometric Tension ◽  
Content Type ◽  
Relaxing Factor ◽  
Vascular Responsiveness ◽  
Basilar Arteries ◽  
Intracranial Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Intimal Lesion ◽  
Endothelium Dependent Relaxation

✓ The effect of hypercholesterolemia on vascular responsiveness was studied in isolated rabbit arteries. The arteries of animals maintained on a cholesterol-rich (1%) diet for 6 months had more pronounced intimal lesion than those receiving the diet for 3 months. The aortas were more severely damaged than the carotid or basilar arteries. Segments of the arteries were mounted in organ chambers for isometric tension recording or for measurement of the endothelium-derived relaxing factor. Endothelium-independent relaxation induced by glyceryl trinitrate was not affected even in the most severely damaged arteries; endothelium-dependent relaxation in response to acetylcholine (ACh) and A23187 was progressively inhibited as the degree of fatty streak formation increased. In the carotid arteries, mean (± standard deviation) relaxation induced by 10−5 M of ACh (expressed as a percentage of the maximum relaxation induced by 10−4 M of papaverine) decreased from 87.33% ± 6.30% in control tissues to 60.90% ± 4.64% in vessels from animals subjected to 6 months of hypercholesterolemia (p < 0.01); in the aortas, mean relaxation due to 10−5 M of ACh was 85.08% ± 8.03% in control tissues and 41.35% ± 13.68% in hypercholesterolemic tissues (p < 0.01). In the carotid arteries, mean relaxation induced by 10−7 M of A23187 decreased from 95.81% ± 3.58% in control tissues to 55.95% ± 2.81% in hypercholesterolemic tissues (p < 0.01); in the aortas, relaxation in response to 10−7 M of A23187 was 73.73% ± 4.35% in control tissues and 29.35% ± 6.77% in hypercholesterolemic tissues (p < 0.01). Intimal lesions were not produced in the basilar arteries even in rabbits with 12 months of hypercholesterolemia, and endothelium-dependent relaxation was preserved.

Lack of endothelium-dependent relaxation in coronary resistance arteries of cholesterol-fed rabbits

1989 ◽  
Vol 256 (3) ◽  
pp. C591-C597 ◽  
Author(s):  
J. A. Osborne ◽  
M. J. Siegman ◽  
A. W. Sedar ◽  
S. U. Mooers ◽  
A. M. Lefer
Keyword(s):  
Control Diet ◽  
Force Production ◽  
Coronary Resistance ◽  
Resistance Arteries ◽  
Contractile Responses ◽  
Relaxing Factor ◽  
Equal Degree ◽  
Maximum Decrease ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation

The endothelium-dependent contractile responses of subepicardial coronary resistance arteries (286 +/- 18 microns ID, n = 22) from rabbits fed either a 0.5 or 2.0% cholesterol-enriched diet or a control diet for 10-12 wk were determined under isometric conditions at the optimum length for active force production (Lo). After the development of tone with 29 mM K+-Krebs, arteries from control rabbits treated with acetylcholine (0.1-10 microM) showed a concentration-dependent relaxation, with a maximum decrease in tone of 63%. In contrast, coronary arteries from animals fed 0.5 and 2.0% cholesterol contracted to acetylcholine (approximately 210% increase in tone). A similar phenomenon was seen with arteries precontracted with 10 nM 9,11-methanoepoxy-prostaglandin H2 (U 46,619), a thromboxane A2 mimetic. The contractile responses to acetylcholine occurred in arteries in which the endothelium was structurally intact and which were devoid of plaque. Arteries from cholesterol-fed animals were poorly responsive to ADP (0.01-10.0 microM), whereas arteries from normal animals relaxed. All arteries relaxed to an equal degree when exposed to acidified nitrite, which produces nitric oxide (NO). The data suggest that as a result of hypercholesterolemia, there may be a dysfunction in the synthesis or release of endothelium-derived relaxing factor (EDRF) by the endothelial cells of coronary resistance arteries, rather than an abnormality of the smooth muscle cells per se.

Tension response of mammalian muscle to intra-arterial acetylcholine

1960 ◽  
Vol 198 (3) ◽  
pp. 507-510 ◽  
Author(s):  
Peter T. Rowley ◽  
Jay B. Wells ◽  
Richard L. Irwin
Keyword(s):  
Dose Response ◽  
Contractile Response ◽  
Tibialis Anterior Muscle ◽  
Arterial Occlusion ◽  
Isometric Tension ◽  
Neural Stimulation ◽  
Dose Response Relationship ◽  
Mammalian Muscle ◽  
Tension Response ◽  
Stimulation Of

Using isometric tension recording of the tibialis anterior muscle of the cat, the response to intra-arterial acetylcholine injection was studied and compared to the response to electrical stimulation of the nerve. The amount of acetylcholine, the rate of injection and the volume of diluent injected are interrelated factors in the production of tension. Regardless of the amount and concentration of the acetylcholine injected, the contractile response of the muscle has a slower rate of rise and a longer duration than the response from single maximal impulse stimulation to the nerve and a maximal tension less than from a tetanic neural stimulation. The dose-response relationship between the injected acetylcholine and the resultant tension and its modification by curare are described. The steep portion of the dose-response curve was found to occur in most experiments between 0.5 and 6.0 µg. A method of supplying blood to the muscle is described which provides more reliable intermittent arterial occlusion during injection.

Endothelium derived relaxing factor release from canine coronary artery by leukocytes

1995 ◽  
Vol 73 (3) ◽  
pp. 404-408 ◽  
Author(s):  
Joseph F. Kleha ◽  
Pierre Devesly ◽  
Anthony Johns
Keyword(s):  
Endothelial Cell ◽  
Coronary Artery ◽  
Human Monocyte ◽  
Relaxing Factor ◽  
Canine Coronary Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583 ◽  
Muscle Calcium ◽  
Endothelium Dependent Relaxation ◽  
Factor Release

Lectins, known to recognize endothelial cell adhesion molecules, have been shown to release endothelium-derived relaxing factor (EDRF) from blood vessels. We investigated the effects of different leukocyte-type cells to determine if these cells, by interacting with the endothelium, could release EDRF from the circumflex branch of the canine coronary artery. The following cells were investigated: human promyelocytic leukemia (HL-60), human monocyte (THP-1), and human Burkitt lymphoma (DAUDI). All of these cells produced a significant endothelium-dependent relaxation of the dog coronary artery in the presence of ibuprofen. The endothelium-dependent relaxations were reversed by hemoglobin (10 μM), methylene blue (3 μM), 6-anilino-5,8-quinolinedione (LY 83583, 30 μM), and NG-nitro-L-arginine methyl ester (L-NAME, 1 mM). HL-60 cells grown in the presence of 1 mM L-NAME retained their ability to cause endothelium-dependent relaxation of the canine coronary artery, suggesting that the source of the NO was the endothelium and not the HL-60 cells. The cell-induced vascular relaxation could be obtained in the absence of extracellular calcium. It is suggested that HL-60, THP-1, and DAUDI cells interact with a specific receptor on the endothelial cell and as a result of this interaction the endothelial cells are stimulated to release EDRF.Key words: endothelium-derived relaxing factor, nitric oxide, endothelium, HL-60, DAUDI, THP-1, smooth muscle, calcium, contraction, canine coronary artery.

Increases in pulse pressure impair acetylcholine-induced vascular relaxation

1995 ◽  
Vol 268 (1) ◽  
pp. H359-H363 ◽  
Author(s):  
S. M. Ryan ◽  
B. J. Waack ◽  
B. L. Weno ◽  
D. D. Heistad
Keyword(s):  
Pulse Pressure ◽  
Carotid Arteries ◽  
Inhibitory Effect ◽  
Isometric Tension ◽  
High Pulse Pressure ◽  
Donor Artery ◽  
Mean Pressure ◽  
High Pulse ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation

Effects of pulse pressure on acetylcholine-induced endothelium-dependent relaxation were investigated using a cascade bioassay model. Intact carotid arteries from rabbits were perfused at constant flow, and activity of endothelium-derived relaxing factor (EDRF) was assayed by measuring changes in isometric tension in a detector ring without endothelium. When pulse pressure of the donor artery was raised from approximately 2 to 10 mmHg, relaxation to acetylcholine (10(-7) M) was reduced from 31 +/- 3 (means +/- SE) to 20 +/- 2% (expressed as percent relaxation of phenylephrine-induced tone). Responses of the detector ring to nitroprusside were unchanged. Superoxide dismutase (SOD) and indomethacin each prevented impairment of relaxation to acetylcholine at high pulse pressure. When the donor artery was perfused at a higher mean pressure, elevation of pulse pressure also impaired relaxation to acetylcholine, and this impairment was prevented by SOD. These findings suggest that elevation of pulse pressure inhibits acetylcholine-induced, endothelium-dependent relaxation, and this inhibitory effect is mediated by generation of oxygen radicals.

Endothelium and mechanical responses of isolated monkey pulmonary veins to histamine

1990 ◽  
Vol 259 (4) ◽  
pp. H1032-H1037 ◽  
Author(s):  
T. Matsuki ◽  
T. Ohhashi
Keyword(s):  
Pulmonary Veins ◽  
Dependent Manner ◽  
High Concentration ◽  
Concentration Dependent Manner ◽  
Mechanical Responses ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
H2 Receptors ◽  
Endothelium Derived Relaxing Factor ◽  
Stimulation Of

Ring strips of monkey pulmonary veins precontracted with a high concentration of prostaglandin F2 alpha (PGF2 alpha) relaxed in a concentration-dependent manner in response to histamine. Treatment with mepyramine and/or famotidine attenuated the relaxation. 2-Pyridylethylamine (2PEA) and dimaprit caused relaxations in the precontracted preparations, which were inhibited by pretreatment with mepyramine and famotidine, respectively. Removal of endothelium reversed the histamine- and 2PEA-induced relaxations to dose-related contractions. On the other hand, the removal had no effect on the dimaprit-induced relaxations, which were significantly reduced by pretreatment with famotidine. Histamine-induced relaxations in the precontracted strips with endothelium in the presence and absence of famotidine were suppressed or abolished by treatment with methylene blue or hemoglobin but were unaffected by aspirin. It may be concluded that histamine-induced relaxation in monkey pulmonary veins precontracted with PGF2 alpha is mediated by H2-receptors in smooth muscle and H1-receptors in endothelium. Also, stimulation of the endothelial H1-receptors liberates an endothelium-derived relaxing factor.

Myogenic autoregulation of flow may be inversely related to endothelium-derived relaxing factor activity

1990 ◽  
Vol 258 (4) ◽  
pp. H1171-H1180 ◽  
Author(s):  
T. M. Griffith ◽  
D. H. Edwards
Keyword(s):  
Negative Slope ◽  
Resistance Arteries ◽  
Flow Rates ◽  
Relaxing Factor ◽  
Flow Perfusion ◽  
Rabbit Ear ◽  
Endothelium Derived Relaxing Factor ◽  
Controlled Flow ◽  
Resting Tone ◽  
Perfusion Mode

The influence of basal endothelium-derived relaxing factor (EDRF) activity on autoregulation was studied under conditions of controlled-flow and controlled-pressure perfusion in the isolated rabbit ear, a weakly autoregulating vascular bed. Hemoglobin and NG-monomethyl-L-arginine were used to inhibit EDRF activity, and in some experiments resting tone was increased by serotonin. The diameters of five generations of resistance arteries (ranging from 70 to 1,000 microns in size) were measured at different flow rates by X-ray microangiography. Diameter-flow (D-Q) relationships were correlated with pressure-flow (P-Q) and conductance-flow (G-Q) relationships. In the presence of EDRF activity no autoregulation was observed, P-Q relationships being linear and G-Q and D-Q relationships common both to controlled-flow and to controlled-pressure modes of perfusion. After inhibition of EDRF activity in constricted preparations, P-Q relationships became sigmoidal in shape in controlled-pressure perfusion mode, reflecting a range of perfusion pressures/flow rates over which they were able to "autoregulate" flow. Over this autoregulatory range the corresponding G-Q and D-Q relationships exhibited regions of negative slope. Autoregulation was not observed in controlled-flow perfusion mode even in the absence of EDRF activity. The findings imply that flow- or pressure-dependent constriction can mediate autoregulation in controlled-pressure mode when not overridden by basal EDRF activity, as normally appears to be the case in these preparations. Differences in autoregulation in different organs may be inversely related to EDRF activity, which is known to differ between vascular beds.

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