Is nitric oxide the only endothelium-derived relaxing factor in canine femoral veins?

1989 ◽  
Vol 257 (6) ◽  
pp. H1910-H1916 ◽  
Author(s):  
V. M. Miller ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Sodium Nitroprusside ◽  
Femoral Vein ◽  
Pulmonary Veins ◽  
Chemical Properties ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583

Nitric oxide may be an endothelium-derived relaxing factor in systemic arteries and pulmonary veins. The endothelium-derived relaxing factor of systemic veins has not been characterized. Experiments were designed to determine whether the endothelium-derived relaxing factor of systemic veins shared chemical properties and mechanisms of action with nitric oxide. Rings of the canine femoral vein with and without endothelium were suspended in organ chambers for the measurement of isometric force. In rings without endothelium, relaxations to nitric oxide were augmented by superoxide dismutase plus catalase and were inhibited by hemoglobin, methylene blue, and LY 83583. The endothelium-dependent relaxations to acetylcholine and A23187 were not augmented by superoxide dismutase plus catalase but were inhibited by hemoglobin and only moderately reduced by either methylene blue or LY 83583. Relaxations to sodium nitroprusside were not inhibited by methylene blue and LY 83583. Relaxations to sodium nitroprusside were inhibited by ouabain and K+-free solution; those to nitric oxide were not. These results indicate that although the endothelium-derived relaxing factor released from canine systemic veins shares some chemical properties with nitric oxide, the mechanism by which relaxations are induced by the two differ. A factor dissimilar to nitric oxide but acting like sodium nitroprusside may be released by the endothelium of canine systemic veins.

Similar responsiveness of smooth muscle of the canine basilar artery to EDRF and nitric oxide

1989 ◽  
Vol 257 (4) ◽  
pp. H1235-H1239 ◽  
Author(s):  
Z. S. Katusic ◽  
J. J. Marshall ◽  
H. A. Kontos ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Basilar Artery ◽  
Inhibitory Effect ◽  
Relaxing Factor ◽  
Basilar Arteries ◽  
Canine Basilar Artery ◽  
Endothelium Derived Relaxing Factor ◽  
Ly 83583 ◽  
Hemoglobin M

Experiments were designed to compare the reactivity of canine basilar arteries to endothelium-derived relaxing factor (EDRF) and nitric oxide. Preparations with endothelium activated by bradykinin were used to study relaxations induced with EDRF, whereas the inhibitory effect of nitric oxide was studied in preparations without endothelium. All experiments were performed in the presence of indomethacin. EDRF- and nitric oxide-induced relaxations were significantly augmented in the presence of superoxide dismutase plus catalase but were reduced in the presence of methylene blue, LY 83583, and hemoglobin. M & B 22984 did not affect relaxations to either EDRF or nitric oxide. These results indicate that in the canine basilar artery EDRF is not an oxygen-derived free radical. The similar responsiveness of the basilar artery to EDRF and nitric oxide is consistent with the proposal that in the canine basilar artery nitric oxide is the 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.

A new relaxing factor in supernatant of incubated rat peritoneal neutrophils

1991 ◽  
Vol 260 (3) ◽  
pp. H967-H972
Author(s):  
K. Kadota ◽  
Y. Yui ◽  
R. Hattori ◽  
H. Uchizumi ◽  
C. Kawai
Keyword(s):  
Methylene Blue ◽  
Superoxide Dismutase ◽  
De Novo ◽  
Polymorphonuclear Neutrophils ◽  
Organ Bath ◽  
Vasoactive Substance ◽  
Cyclic Monophosphate ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

It was found that when rat peritoneal neutrophils were added to an organ bath, they released an unstable vasoactive substance designated as neutrophil-derived relaxing factor (NDRF), which is similar to endothelium-derived relaxing factor. Besides NDRF, a more stable (activity maintained for at least 7 days at -80 degrees C) relaxing factor was found to be generated in the supernatant after the incubation of rat peritoneal neutrophils in buffer. This supernatant relaxing factor (SRF) induced an increase in the guanosine 3',5'-cyclic monophosphate content of aortic strips. Its relaxing activity was potentiated by superoxide dismutase. It was inhibited by hemoglobin, hydroquinone, or methylene blue but not by catalase or mannitol. Preincubation of polymorphonuclear neutrophils with aspirin, quinacrine, metyrapone, or AA-861 had no effect on the relaxing activity of SRF. L-Arginine dose dependently increased the relaxing activity of SRF, whereas NG-monomethyl-L-arginine (L-NMMA) decreased it, and this decrease was reversed by L-arginine. In contrast, neither L-arginine nor L-NMMA affected the relaxing activity of NDRF. These data suggest that SRF may represent a relaxing factor that is synthesized de novo from L-arginine.

Inhibition of vascular nitric oxide-cGMP pathway by plasma from ischemic hindlimb of rats

1995 ◽  
Vol 269 (1) ◽  
pp. H254-H261 ◽  
Author(s):  
J. S. Jin ◽  
R. C. Webb ◽  
L. G. D'Alecy
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Superoxide Dismutase ◽  
Contractile Activity ◽  
Femoral Vein ◽  
Guanylate Cyclase Activity ◽  
Cgmp Pathway ◽  
Induced Hypertension ◽  
Control Plasma

The hypothesis was tested that plasma from ischemic hindlimbs facilitates hypertension. Ischemia-induced hypertension was generated in rats by infrarenal aortic cross clamping for 5 h after which plasma was obtained from femoral vein blood. In vitro contractile activity of naive aortic rings incubated for 2 h in plasma collected from ischemic rats demonstrated reduced relaxation to acetylcholine and nitroglycerin. Methylene blue (10(-5) M) induced greater contraction in rings incubated in control vs. ischemic plasma, suggesting that endogenous guanylate cyclase activity is decreased by ischemic plasma. However, 8-bromo-guanosine 3',5'-cyclic monophosphate (cGMP) relaxed equally strips incubated in ischemic or control plasma. Acetylcholine-induced nitrite release was significantly lower in ischemic vs. control plasma-incubated strips (8.6 +/- 2.7 vs. 28.2 +/- 2.3 ng/10 mg tissue wt, respectively). The impaired relaxation to acetylcholine in ischemic plasma-incubated rings was significantly increased by L-arginine but not by prior treatment of ischemic plasma with heating or superoxide dismutase and catalase. These findings suggest the impaired relaxation is mediated through inhibition of the nitric oxide-cGMP pathway. Prolonged blunting of vasodilation by ischemic plasma may therefore contribute to maintenance of a sustained vasoconstriction and ischemic hypertension.

Repeated endothelial removal augments intimal thickening and attenuates EDRF release

1994 ◽  
Vol 266 (4) ◽  
pp. H1348-H1356 ◽  
Author(s):  
Y. Niimi ◽  
H. Azuma ◽  
K. Hirakawa
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Carotid Arteries ◽  
Intimal Thickening ◽  
Endothelial Regeneration ◽  
Relaxing Factor ◽  
Endothelial Denudation ◽  
Endothelium Derived Relaxing Factor ◽  
Relaxation Responses ◽  
Progression Of Atherosclerosis

To evaluate the significance of repeated denudation injury in progression of atherosclerosis, we performed a single and then a second balloon denudation on the rabbit carotid arteries. Morphological examinations and organ chamber experiments were performed, and the results were compared. On morphological examinations, reendothelialization was almost completed in 2 wk after redenudation, whereas it required 6 wk after a single denudation. Intimal thickening progressed after redenudation. Organ chamber experiments showed that contractile responses and endothelium-independent relaxation remained unchanged after redenudation. Endothelium-dependent relaxations to acetylcholine, ADP, and substance P decreased progressively by repeating denudation. These relaxation responses were inhibited by NG-nitro-L-arginine, hemoglobin, and methylene blue and were considered to be associated with the production and/or release of endothelium-derived relaxing factor-nitric oxide (EDRF-NO). The diffusion barrier mechanism for the decreased endothelium-dependent relaxations was ruled out using sandwich experiments. In conclusion, repeated endothelial denudation caused progression of intimal thickening and acceleration of endothelial regeneration, and repeated endothelial regeneration resulted in progressively less production and/or release of EDRF-NO.

Inhibition of rat mesangial cell mitogenesis by nitric oxide-generating vasodilators

1989 ◽  
Vol 257 (1) ◽  
pp. F60-F66 ◽  
Author(s):  
U. C. Garg ◽  
A. Hassid
Keyword(s):  
Nitric Oxide ◽  
Sodium Nitroprusside ◽  
Culture Medium ◽  
Mesangial Cell ◽  
Mesangial Cells ◽  
Inhibitory Effect ◽  
Relaxing Factor ◽  
Growth Inhibitory ◽  
Endothelium Derived Relaxing Factor

Recent studies indicate that endothelium-derived relaxing factor (EDRF) may be identical with nitric oxide (NO). The purpose of this study was to investigate the antimitogenic effect of NO-generating drugs in cultured mesangial cells. S-nitroso-N-acetylpenicillamine, sodium nitroprusside, and isosorbide dinitrate, which generate NO, dose dependently inhibited serum-stimulated DNA synthesis. All three drugs also inhibited the rate of cell proliferation, whereas sodium nitroprusside and S-nitroso-N-acetylpenicillamine decreased cell density at confluence. The antimitogenic activity of S-nitroso-N-acetylpenicillamine was labile in culture medium and could be inhibited by hemoglobin, supporting the view that NO, in free or bound form, was the ultimate effector. All three vasodilators increased cellular guanosine 3',5'-cyclic monophosphate (cGMP) levels dose dependently; moreover, 8-bromo-cGMP mimicked the effects of the NO-generating drugs, suggesting that cGMP may be an intracellular mediator of antimitogenesis. The growth-inhibitory effect of S-nitroso-N-acetylpenicillamine was reversible and was not due to cell toxicity as shown by several criteria of cell viability. The results raise the possibility that EDRF/NO may be a modulator of mesangial cell growth in vivo.

Independent blockade of cerebral vasodilation from acetylcholine and nitric oxide

1988 ◽  
Vol 255 (4) ◽  
pp. H847-H854 ◽  
Author(s):  
J. J. Marshall ◽  
E. P. Wei ◽  
H. A. Kontos
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Oxygen Radicals ◽  
Nitro Blue Tetrazolium ◽  
Cerebral Microcirculation ◽  
Relaxing Factor ◽  
Blue Tetrazolium ◽  
Endothelium Derived Relaxing Factor ◽  
Cerebral Vasodilation ◽  
Mediated Oxidation

We investigated the mechanisms of cerebral arteriolar dilation from topical acetylcholine and the nitrovasodilators, sodium nitroprusside, nitroglycerin, and nitric oxide, in anesthetized cats equipped with cranial windows for the observation of the cerebral microcirculation. Acetylcholine-mediated dilation was eliminated by topical methylene blue. This blockade was reversed by either topical superoxide dismutase, catalase, or deferoxamine. Nitroprusside- and nitric oxide-induced dilation were not affected by methylene blue. Vasodilation from the nitrovasodilators was significantly diminished by topical nitro blue tetrazolium, but acetylcholine-mediated dilation was unaffected by nitro blue tetrazolium. Neither methylene blue nor nitro blue tetrazolium affected dilation from topical 8-bromoguanosine 3',5'-cyclic monophosphate. These data show that methylene blue selectively blocks acetylcholine-mediated endothelium-dependent dilation by generating oxygen radicals. The mechanism involved is hydroxyl radical-mediated oxidation of endothelium-derived relaxing factor. Nitro blue tetrazolium selectively blocks dilation from the endothelium-independent nitrovasodilators. The endothelium-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is not nitric oxide.

Proximal and distal dog coronary arteries respond differently to basal EDRF but not to NO

1989 ◽  
Vol 256 (3) ◽  
pp. H828-H831 ◽  
Author(s):  
U. Hoeffner ◽  
C. Boulanger ◽  
P. M. Vanhoutte
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Sodium Nitroprusside ◽  
Coronary Arteries ◽  
Relaxing Factor ◽  
Prostaglandin F2 Alpha ◽  
Endothelium Derived Relaxing Factor

Experiments were designed to analyze the effects of endothelium-derived relaxing factor(s) (EDRF; released basally or on stimulation with acetylcholine) and nitric oxide (NO) on smooth muscle of coronary arteries of different diameter. During contractions of the bioassay ring evoked with prostaglandin F2 alpha, the relaxations caused by basal EDRF were greater in the distal than in the proximal coronary arteries, whereas there was no difference in response to the EDRF released by acetylcholine. During direct superfusion, NO caused similar relaxations in proximal and distal coronary artery rings. Optimal tension, prostaglandin F2 alpha-induced contractions, and relaxations caused by sodium nitroprusside were comparable in both preparations. In rings of proximal and distal coronary artery studied in organ chambers, acetylcholine caused comparable endothelium-dependent, whereas sodium nitroprusside and NO cause comparable endothelium-independent relaxations. These experiments indicate a difference in response of different-sized coronary arteries to basally released EDRF and suggest that the basally released factor differs from NO.

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