Pressure Depresses the Release of Endothelium-Derived Relaxing Factor from Isolated Canine Carotid Arteries

2015 ◽  
pp. 14-19
Author(s):  
Ana D. Freay ◽  
Anthony Johns ◽  
Cornells van Breemen ◽  
Gabor M. Rubanyi
Keyword(s):  
Carotid Arteries ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

Endothelium-derived relaxing factor inhibits norepinephrine contraction of fetal guinea pig arteries

1993 ◽  
Vol 264 (4) ◽  
pp. H1139-H1145 ◽  
Author(s):  
L. P. Thompson ◽  
C. P. Weiner
Keyword(s):  
Vascular Tone ◽  
Carotid Arteries ◽  
Isometric Contractions ◽  
Maximal Contraction ◽  
Alpha Adrenoceptor ◽  
Relaxing Factor ◽  
Before And After ◽  
Endothelium Derived Relaxing Factor ◽  
Near Term

As in the adult circulation, the endothelium may play an important role in determining fetal vascular tone. The purpose of this study was to determine the influence of the endothelium on norepinephrine- and phenylephrine-induced contraction of pulmonary and carotid arteries from near-term fetal guinea pigs. Isometric contractions of isolated rings to the cumulative addition of norepinephrine (10(-9)-10(-5) M) were measured before and after 1) endothelium removal, 2) NG-monomethyl-L-arginine (L-NMMA; 10(-4) M) to inhibit endothelium-derived relaxing factor (EDRF), 3) methylene blue (10(-5) M) to inhibit guanylate cyclase, 4) oxyhemoglobin (3 x 10(-6) M) to bind EDRF, and 5) indomethacin (10(-5) M) to inhibit cyclooxygenase. All treatment effects were measured in endothelium-intact segments. The maximal norepinephrine contraction of fetal pulmonary (40 +/- 8% KCl, n = 7) and carotid (13 +/- 7% KCl, n = 7) arteries was much less (P < 0.05) than the maximal contraction to 120 mM KCl. Treatments that inhibit the action of EDRF increased contraction of both fetal pulmonary and carotid arteries. L-NMMA also increased contraction to phenylephrine. Indomethacin had no effect on the contractile responses to norepinephrine of either artery. Thus EDRF inhibits alpha-adrenoceptor-stimulated contraction of fetal pulmonary and carotid arteries and may attenuate the constrictor responsiveness of the fetal circulation in vivo.

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.

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.

Interaction of human platelets and leukocytes in modulation of vascular tone

1994 ◽  
Vol 266 (5) ◽  
pp. H1706-H1714 ◽  
Author(s):  
S. Kaul ◽  
B. J. Waack ◽  
R. C. Padgett ◽  
R. M. Brooks ◽  
D. D. Heistad
Keyword(s):  
Superoxide Anion ◽  
Polymorphonuclear Leukocytes ◽  
Vascular Tone ◽  
Carotid Arteries ◽  
Human Platelets ◽  
Vasomotor Tone ◽  
Relaxing Factor ◽  
In Vitro Activation ◽  
Endothelium Derived Relaxing Factor

We tested the hypothesis that the vasodilator response to human platelets is modulated by polymorphonuclear leukocytes (PMNs). Responses to platelets activated with thrombin, as well as PMNs activated with N-formylmethionyl-leucyl-phenylalanine (FMLP), were examined in perfused rabbit carotid arteries in vitro. Activation of platelets produced marked dilatation, and activation of PMNs produced modest constriction in arteries preconstricted with phenylephrine. Vasodilator responses to platelets were greatly impaired during infusion of activated PMNs. Pretreatment of PMNs with superoxide dismutase (SOD) partially restored dilator responses to platelets. Because SOD only partially restored vasodilator responses to platelets, we tested the possibility that adenosine-diphosphatase (ADPase) activity of PMNs may degrade ADP released by platelets and thus reduce vasodilator responses. After incubation with PMNs, dilator responses to ADP, but not acetylcholine, were significantly impaired. These findings indicate that vasodilatation produced by activated human platelets is profoundly impaired by activated leukocytes. We conclude that two mechanisms may account for this effect: 1) endothelium-derived relaxing factor, released in response to platelet-derived ADP, is inactivated by superoxide anion generated by activated PMNs and 2) ADP is degraded by ADPase activity of PMNs. We speculate that platelet-leukocyte interaction may have important effects on vasomotor tone.

Anti-EDRF effect of tumor necrosis factor in isolated, perfused cat carotid arteries

1989 ◽  
Vol 256 (5) ◽  
pp. H1509-H1512 ◽  
Author(s):  
N. Aoki ◽  
M. Siegfried ◽  
A. M. Lefer
Keyword(s):  
Tumor Necrosis Factor ◽  
Tumor Necrosis ◽  
Carotid Arteries ◽  
Human Tumor ◽  
Vasodilator Response ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor ◽  
Inhibitor Of Protein Synthesis ◽  
Necrosis Factor ◽  
Factor Release

Cat carotid arteries that have an intact endothelium were isolated and perfused with Krebs-Henseleit solution containing recombinant human tumor necrosis factor (rhTNF). Perfused arteries were preconstricted with KCl and then dilated with acetylcholine (ACh) or acidified NaNO2. After perfusion with TNF (4 micrograms/ml) for 120 min, the ACh-induced vasodilator response was markedly blunted, but the NaNO2 vasodilator response was not significantly affected. Arteries perfused with 2 micrograms/ml TNF for 60-120 min or with 4 micrograms/ml for 60 min did not develop a significantly impaired relaxation to ACh. Moreover, perfusion with 20-100 micrograms/ml cycloheximide, an inhibitor of protein synthesis, blocked the TNF-induced impairment of the relaxation to ACh. On the other hand, the vasodilator response to acidified NaNO2 did not change in any perfused carotid arteries. These results suggest that TNF promotes the synthesis of proteins that contribute to the damage of endothelial cells directly, probably by inhibiting endothelium-derived relaxing factor release.

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).

Why is a new journal dedicated to vascular biology required?

2018 ◽  
Author(s):  
Paolo Madeddu
Keyword(s):  
Myocardial Ischemia ◽  
Tumor Growth ◽  
Vascular Tone ◽  
50Th Anniversary ◽  
Vascular Biology ◽  
Active Process ◽  
Master Regulators ◽  
Relaxing Factor ◽  
Tissue Healing ◽  
Endothelium Derived Relaxing Factor

The year 2018 marked the 110th anniversary of Goldmann’s discovery that vascularization is an active process in tissues1 and the 50th anniversary of the concomitant reports from Greenblatt and Shubik2 and Ehrmann and Knoth3 that soluble morphogenic factors are required for cancer angiogenesis. Many other radically transformative paradigms have been introduced in the last decades. To name a few, the molecular search for the identity of master regulators of vascular tone led to the discovery of the Endothelium-Derived Relaxing Factor (EDRF; i.e., NO4), while clinically inspired investigations led to the recognition of the pathophysiological relevance of neoangiogenesis in cancer and tissue healing. This brought about the proposal of blocking angiogenesis to halt tumor growth and stimulating angiogenesis to treat myocardial ischemia and heart failure5-7.

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.

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