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.

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.

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.

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.

Endothelium-dependent pressure-induced contraction of isolated canine carotid arteries

1988 ◽  
Vol 255 (4) ◽  
pp. H783-H788 ◽  
Author(s):  
G. M. Rubanyi
Keyword(s):  
Methylene Blue ◽  
Coronary Artery ◽  
Carotid Artery ◽  
Carotid Arteries ◽  
Elevated Pressure ◽  
Relaxing Factor ◽  
Donor Segment ◽  
Artery Segment ◽  
Canine Coronary Artery ◽  
Endothelium Derived Relaxing Factor

Experiments were conducted in a bioassay system, where a canine coronary artery ring without endothelium (bioassay tissue) was superfused by the effluent from a perfused canine carotid artery segment with endothelium (donor segment). A rapid increase in transmural pressure (from near 0 to 32-38 mmHg) triggered active contraction of the donor segment and simultaneously of the bioassay tissue. These contractions were prevented by removal of the endothelium from the donor segment but not by treatment of the segment with indomethacin. Exposure to elevated pressure depressed basal, acetylcholine-, and flow-induced release of endothelium-derived relaxing factor(s). Methylene blue prevented the pressure-induced contraction of the bioassay ring. These data show that pressure-induced contraction of isolated carotid arteries is endothelium dependent and is mediated by the depression of the synthesis and/or release of endothelium-derived relaxing factor(s).

Occurrence of endothelium-derived relaxing factor – nitric oxide in the lamb ductus arteriosus

1994 ◽  
Vol 72 (1) ◽  
pp. 82-88 ◽  
Author(s):  
Flavio Coceani ◽  
Lois Kelsey ◽  
Eric Seidlitz
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Ductus Arteriosus ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Prostaglandin E ◽  
Antiinflammatory Drugs ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Near Term ◽  
Nitric Oxide Inhibitors

To determine whether the ductus arteriosus can form endothelium-derived relaxing factor – nitric oxide, we used isolated ductal strips from near-term fetal lamb and examined their response to bradykinin (a nitric oxide stimulator), L-arginine (a nitric oxide precursor), and agents interfering with the synthesis (Nω-nitro-L-arginine) and action (methylene blue) of nitric oxide. Bradykinin relaxed the indomethacin-contracted ductus dose dependently from a threshold of about 10−10 M, and peak relaxation was greater at high (176–210 mmHg; 1 mmHg = 133.3 Pa) than low (15–25 mmHg) [Formula: see text]. Bradykinin relaxation was nearly completely or completely abolished in endothelium-denuded preparations and, in its place, there was often a small contraction. Pretreatment with nitric oxide inhibitors also prevented, in part (methylene blue, 1 μM) or in full (Nω-nitro-L-arginine, 100 μM), the relaxant effect of bradykinin. Paradoxically, L-arginine (10 μM) had an inhibiting rather than an enhancing effect on the bradykinin relaxation. Nω-Nitro-L-arginine (100 μM) and methylene blue (1–100 μM) contracted by themselves the untreated ductus, and their action persisted after removal of the endothelium. These findings indicate the presence in the ductus arteriosus of a nitric oxide based relaxing mechanism, which may supplement prostaglandin E2 in keeping the vessel patent in the fetus. This mechanism may, on one hand, afford protection against nonsteroidal antiinflammatory drugs in utero and may, on the other hand, complicate the management of prematures with persistent ductus and account for failures of the indomethacin therapy.Key words: ductus arteriosus patency and closure, endothelium-derived relaxing factor – nitric oxide, prostaglandin.

Modulation of cerebral arterial tone by endothelium-derived relaxing factor

1993 ◽  
Vol 264 (4) ◽  
pp. H1245-H1250 ◽  
Author(s):  
J. E. Brian ◽  
R. H. Kennedy
Keyword(s):  
Nitric Oxide ◽  
Muscle Tone ◽  
Cerebral Arteries ◽  
Maximum Tension ◽  
Relaxing Factor ◽  
Middle Cerebral Arteries ◽  
Endothelium Derived Relaxing Factor ◽  
Vascular Smooth Muscle Tone ◽  
Dose Dependent ◽  
Arterial Tone

This study was designed to further elucidate the role of the endothelium in regulation of cerebral vascular smooth muscle tone. Dose-dependent vasoconstrictive effects of serotonin (5-HT) were examined in endothelium-intact and endothelium-denuded ring segments prepared from canine basilar and middle cerebral arteries. Some preparations were pretreated with 10(-5) M N omega-nitro-L-arginine (L-NNA), an agent that inhibits the production of L-arginine-derived nitric oxide, one of the compounds proposed to be endothelium-derived relaxing factor. L-NNA alone elicited marked dose-dependent increases in tension in endothelium-intact preparations; a significantly smaller response was seen in endothelium-denuded preparations. The effects of L-NNA on endothelium-intact preparations were partially reversed by washing and treatment with L-arginine. The maximum tension induced by 5-HT was approximately doubled by removal of the endothelium as well as by L-NNA treatment of endothelium-intact preparations; a slight increase in maximum tension occurred in endothelium-denuded preparations treated with L-NNA. The concentration of 5-HT producing half-maximal contraction (ED50) was not affected by L-NNA. These data suggest that L-arginine-derived nitric oxide modulates canine cerebral arterial tone in both the resting state and during contraction with 5-HT.

Endothelial Dysfunction in Shock States

Physiology ◽  
1993 ◽  
Vol 8 (4) ◽  
pp. 145-148 ◽  
Author(s):  
AGB Kovach ◽  
AM Lefer
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Tissue Injury ◽  
Circulatory Shock ◽  
Relaxing Factor ◽  
Vascular Beds ◽  
Endothelium Derived Relaxing Factor

Circulatory shock results in dysfunction of the endothelium in various vascular beds. This dysfunction is characterized by marked impairment in the vasculature's ability to relax to endothelium-dependent vasodilators. This loss of endothelium-derived relaxing factor, or nitric oxide, leads to profound tissue injury.

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.

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