scholarly journals Superoxide anions and hyperoxia inactivate endothelium-derived relaxing factor

1986 ◽  
Vol 250 (5) ◽  
pp. H822-H827 ◽  
Author(s):  
G. M. Rubanyi ◽  
P. M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Biological Activity ◽  
Free Radicals ◽  
Protective Effect ◽  
Femoral Artery ◽  
Superoxide Anions ◽  
Relaxing Factor ◽  
Oxygen Derived Free Radicals ◽  
Endothelium Derived Relaxing Factor

Experiments were designed to determine the effects of oxygen-derived free radicals on the production and biological activity of endothelium-derived relaxing factor or factors released by acetylcholine. Rings of canine coronary arteries without endothelium (bioassay rings) were superfused with solution passing through a canine femoral artery with endothelium. Superoxide dismutase caused maximal relaxation of the bioassay ring when infused upstream, but not downstream, of the femoral artery; this effect of superoxide dismutase was inhibited by catalase. Infusion of acetylcholine relaxed the bioassay rings because it released a labile relaxing factor (or factors) from the endothelium. When infused below the femoral artery, superoxide dismutase and, to a lesser extent, catalase augmented the relaxations to acetylcholine. Superoxide dismutase, but not catalase, doubled the half-life of the endothelium-derived relaxing factor(s). This protective effect of the enzyme was augmented fivefold by lowering the oxygen content of the perfusate from 95 to 10%. These data demonstrate that: superoxide anions inactivate the relaxing factor(s) released by acetylcholine from endothelial cells and hyperoxia favors the inactivation of endothelium-derived relaxing factor(s).

Bioassay of endothelium-derived relaxing factor(s): inactivation by catecholamines

1985 ◽  
Vol 249 (1) ◽  
pp. H95-H101 ◽  
Author(s):  
G. M. Rubanyi ◽  
R. R. Lorenz ◽  
P. M. Vanhoutte
Keyword(s):  
Endothelial Cells ◽  
Femoral Artery ◽  
Physiological Salt Solution ◽  
Second Phase ◽  
Partial Recovery ◽  
Rapid Phase ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
Bioassay Technique ◽  
Endothelium Derived Relaxing Factor

A bioassay technique was developed to analyze the effect of vasoactive substance(s) released from endothelial cells. Canine femoral arteries with or without endothelium were perfused with physiological salt solution at 37 degrees C. The perfusate was bioassayed with a ring of coronary artery without endothelium. A substance(s) released by the endothelial cells under basal conditions caused relaxation of unstimulated coronary arteries or relaxation of those contracted with prostaglandin F2 alpha. The release of the relaxing substance(s) was augmented by acetylcholine. The relaxation induced by acetylcholine was biphasic: an initial rapid phase followed by a partial recovery and a slowly developing prolonged relaxation; the half-life of the substance(s) causing the initial phase averaged 6.3 s. Norepinephrine, epinephrine, and ascorbic acid, given downstream of the femoral artery, reversibly prevented the second phase but only attenuated the initial relaxation. These observations indicate that an endothelium-derived relaxing substance(s) is released into the lumen of the femoral artery under basal conditions and during stimulation with acetylcholine. Catecholamines can inactivate the relaxing substance(s) but do not prevent either its production by endothelial cells or its action on vascular smooth muscle.

Release of intact endothelium-derived relaxing factor depends on endothelial superoxide dismutase activity

1991 ◽  
Vol 260 (2) ◽  
pp. C219-C225 ◽  
Author(s):  
A. Mugge ◽  
J. H. Elwell ◽  
T. E. Peterson ◽  
D. G. Harrison
Keyword(s):  
Endothelial Cells ◽  
Superoxide Dismutase ◽  
Nitrogen Oxides ◽  
Antioxidant Defense ◽  
Rabbit Aorta ◽  
Biologically Active ◽  
Relaxing Factor ◽  
Vasodilator Activity ◽  
Endothelium Derived Relaxing Factor

Endothelium-derived relaxing factor (EDRF) is rapidly inactivated by radicals. Endothelial cells possess several antioxidant defense mechanisms. It is not clear which intrinsic antioxidant defense systems are important to preserve the release of biologically active EDRF. We impaired antioxidant defense in normal vascular tissue by inhibiting catalase activity with 3-amino-1,2,4-triazole (AT), superoxide dismutase with diethyldithiocarbamate (DETC), and by reducing glutathione content via inhibiting glutathione synthesis with L-buthionine-(S,R)-sulfoximine (BSO). Pretreatment of rabbit aorta in vitro with DETC markedly reduced endothelium-dependent relaxation in response to acetylcholine and calcium ionophore A23187 and, to a lesser extent, reduced endothelium-independent relaxation in response to nitroprusside. Pretreatment of cultured bovine aortic endothelial cells (BAEC) with DETC did not alter release of nitrogen oxides (measured by chemiluminescence), but, the effluent of pretreated cells showed marked depression in vasodilator activity (measured by bioassay). Pretreatment of rabbit aorta in vitro with AT did not alter endothelium-dependent and -independent relaxations. Pretreatment of BAEC with BSO did not alter the release of nitrogen oxides or the vasodilator activity. These results suggest that endothelial superoxide dismutase activity, but not catalase or glutathione, is necessary for the release of biologically active EDRF. An imbalance of the intrinsic superoxide dismutase and the production of superoxide anions may therefore predispose to impaired endothelium-dependent relaxations and alter vascular reactivity.

Regulation of spontaneous EDRF release in diabetic rat aorta by oxygen free radicals

1992 ◽  
Vol 263 (1) ◽  
pp. H257-H265 ◽  
Author(s):  
P. Langenstroer ◽  
G. M. Pieper
Keyword(s):  
Free Radicals ◽  
Oxygen Free Radicals ◽  
Muscle Tone ◽  
Aortic Ring ◽  
Rat Aorta ◽  
Diabetic Rat ◽  
Relaxing Factor ◽  
Oxygen Derived Free Radicals ◽  
Endothelium Derived Relaxing Factor ◽  
Vascular Smooth Muscle Tone

The interaction of endothelium-derived relaxing factor (EDRF) and oxygen-derived free radicals may potentially play an important role in the pathophysiology of complications associated with diabetes. In the present study, we investigated spontaneous EDRF release in diabetic rat aorta that is unmasked by the addition of superoxide dismutase (SOD). SOD produced a significantly greater relaxation in diabetic aorta compared with control aorta using both aortic ring and bioassay preparations. This relaxation was unaltered by pretreatment with catalase or indomethacin. Removal of the endothelium or pretreatment with either NG-monomethyl-L-arginine or methylene blue eliminated SOD-induced relaxation in both control and diabetic rings. Measurement of antioxidant enzymes revealed an elevation in catalase in diabetic aorta, with no difference in the SOD or glutathione peroxidase activity. The increase in catalase activity suggests increased exposure of diabetic aorta to hydrogen peroxide. Pretreatment of rings with the catalase inhibitor, 3-amino-1,2,4-triazole, attenuated the SOD-induced relaxation in diabetic aortic rings but had no effect in control aortic rings. In summary, our observations suggest that the diabetic rat aorta releases more spontaneous EDRF than control aorta; however, the activity of EDRF on vascular smooth muscle tone is masked by increased destruction by oxygen-derived free radicals.

Effect of Superoxide Dismutase on Endothelium-Dependent Relaxation of Aorta from Endotoxin-Treated Rabbits

1994 ◽  
Vol 22 (2) ◽  
pp. 113-120 ◽  
Author(s):  
H Yaku ◽  
K Mikawa ◽  
K Nishina ◽  
N Maekawa ◽  
H Obara
Keyword(s):  
Superoxide Dismutase ◽  
Protective Effect ◽  
Treated Group ◽  
Endothelial Damage ◽  
Histological Studies ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation

To assess the protective effect of superoxide dismutase (SOD) on the endothelium of aorta in endotoxaemia, we investigated the production of endothelium-derived relaxing factor in aorta obtained from endotoxin-treated rabbits concomitantly receiving SOD or not. Thirty-two male Japanese white rabbits were randomly divided into four groups ( n = 8 for each group): one group receiving saline as a placebo, a second receiving 5 mg/kg endotoxin intravenously, a third receiving 5 mg/kg endotoxin intravenously plus SOD, and a fourth receiving SOD alone. SOD was injected intravenously at a dose of 10 000 U/kg before the endotoxin and was infused continuously at a rate of 15 000 units/kg/h throughout the experiment. The tension of the aorta was recorded in vitro 6 h after the start of in vivo treatment with endotoxin or saline. In the aorta of rabbits receiving endotoxin alone, acetylcholine-induced relaxation was reduced by 50%. The SOD fully restored the reduction of acetylcholine-induced relaxation by endotoxin. Histological studies using photomicroscopy revealed endothelial damage in the endotoxin-treated aorta, which was attenuated in the SOD-treated group. These data suggest that intravenous SOD may be an effective treatment for unstable haemodynamics in endotoxaemia.

Acute compensation to abrupt occlusion of rat femoral artery is prevented by NO synthase inhibitors

1994 ◽  
Vol 267 (6) ◽  
pp. H2523-H2530 ◽  
Author(s):  
J. L. Unthank ◽  
J. C. Nixon ◽  
M. C. Dalsing
Keyword(s):  
Femoral Artery ◽  
Arterial Occlusion ◽  
Artery Occlusion ◽  
No Synthase ◽  
Artery Blood Flow ◽  
Relaxing Factor ◽  
Femoral Artery Occlusion ◽  
Before And After ◽  
Endothelium Derived Relaxing Factor ◽  
Oxide Synthase

The hemodynamic significance of endothelium-derived relaxing factor (EDRF)-mediated mechanisms in vascular responses to abrupt rat femoral artery occlusion was investigated. Temporary arterial occlusion was produced before and after inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA). Iliac artery blood flow and arterial pressures proximal and distal to the occlusion were measured. Normal vascular compensation included a return of resistance to preocclusion levels and a rise in distal pressure to a plateau within 5 min postocclusion. After treatment with L-NAME and L-NMMA, postocclusion resistance remained elevated by 53 and 36%, respectively. Collateral dilation after occlusion, as indicated by the rise in distal pressure, was prevented by L-NAME but not L-NMMA. Increases in adrenergic tone and mean arterial pressure by phenylephrine did not prevent compensation, suggesting the effects of L-NAME and L-NMMA did not result from elevated sympathetic activation or pressure. The results are consistent with the hypothesis that the stimulated release of endothelium-derived relaxing factor mediates the acute vascular compensation to abrupt arterial occlusion.

scholarly journals Inhibition by l-glutamine of the release of endothelium-derived relaxing factor from cultured endothelial cells

1990 ◽  
Vol 101 (2) ◽  
pp. 237-239 ◽  
Author(s):  
Markus Hecker ◽  
Jane A. Mitchell ◽  
Tomasz A. Swierkosz ◽  
William C. Sessa ◽  
John R. Vane
Keyword(s):  
Endothelial Cells ◽  
Relaxing Factor ◽  
Cultured Endothelial Cells ◽  
Endothelium Derived Relaxing Factor

Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

1990 ◽  
Vol 258 (1) ◽  
pp. F162-F167 ◽  
Author(s):  
P. J. Shultz ◽  
A. E. Schorer ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Mesangial Cells ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Functional Responses ◽  
Cross Sectional ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

Enhanced release of endothelium-derived factor(s) by chronic increases in blood flow

1988 ◽  
Vol 255 (3) ◽  
pp. H446-H451 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Blood Flow ◽  
Smooth Muscle ◽  
Arteriovenous Fistula ◽  
Muscarinic Receptors ◽  
Femoral Artery ◽  
Response Curves ◽  
Femoral Arteries ◽  
Relaxing Factor ◽  
Bioassay System ◽  
Endothelium Derived Relaxing Factor

Chronic increases in blood flow caused by an arteriovenous fistula augment endothelium-dependent relaxations to acetylcholine. To determine whether endothelial muscarinic receptors are altered, concentration-response curves to acetylcholine were obtained in the presence of pirenzepine in fistula- and sham-operated canine femoral arteries. Pirenzepine inhibited the response to acetylcholine in both arteries. The pA2 (log Kb) for the antagonist was the same. A bioassay system was used to assess release of endothelium-derived relaxing factor. Rings of femoral artery (without endothelium) from unoperated dogs relaxed more when superfused with perfusate derived from endothelium of fistula-operated arteries during acetylcholine stimulation. Rings without endothelium of sham- and fistula-operated arteries relaxed to the same extent when superfused with perfusate derived from the endothelium of unoperated femoral arteries. These results suggest that augmented relaxations to acetylcholine in canine arteries where blood flow is chronically elevated do not result from changes in the subtype of endothelial muscarinic receptors or in the sensitivity of the underlying smooth muscle to endothelium-derived relaxing factor(s). They are likely due to increased release of endothelium-derived relaxing factor(s) on muscarinic activation.

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