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PubMed1992

Role of endothelium in the response of the vein wall to magnesium withdrawal.

Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In noradrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5 x 10(-6) M), and in vessels without endothelium, lowering the magnesium concentration caused a dose-dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Depressed endothelium-dependent relaxation in hypertension: relation to increased blood pressure and reversibility.

Endothelium-dependent relaxation effects have been reported to be impaired in thoracic aorta from genetic and experimentally induced hypertensive rats. This study extends these observations to carotid artery and abdominal aorta from renovascular hypertensive rats. It was also found that rats with coarctation of aorta show depressed endothelium-dependent relaxation responses in thoracic aorta above the stenosis (high pressure region) while no depressed responses are observed in abdominal aorta below the stenosis (normal pressure region). Reversibility of the depression of endothelium-dependent relaxation was investigated on aorta from renovascular hypertensive rats in which blood pressure was normalized by removal of the stenotic kidney three months after induction of hypertension. Endothelium-dependent responses were restored partially after 1-2 weeks and completely after two months of normalization of blood pressure. These results indicate that the increased blood pressure is indeed the causative factor responsible for the impaired endothelium-dependent relaxations in arteries from experimental hypertensive rats, a phenomenon which is reversible, at least in our experimental conditions.

Acetylcholine↗
PubMed1985

Ultrastructural localization of lectin receptors on cerebral endothelium.

Oligosaccharide residues on the endothelial luminal plasma membrane of rat cerebral cortical vessels were localized using biotinylated lectins. In addition, the effect of pretreatment of brain slices with neuraminidase prior to the binding of cationized ferritin (CF) and certain lectins was studied. Conjugates of biotinylated lectins and avidin-D horseradish peroxidase reaction product were evenly distributed on the endothelium of arterioles, capillaries, and venules. Lectin binding sites were observed on the plasma membrane of pinocytotic vesicles open onto the vascular lumen and at the luminal end of the interendothelial space only. The following sugar residues were localized: alpha-D-mannosyl, alpha-D-glucosyl, beta-N-acetylglucosaminyl, sialyl, D-galactosyl, alpha-L-fucosyl, and alpha-N-acetyl-D-galactosaminyl. Following pretreatment of brain slices with neuraminidase beta-D-gal-(1-3)-D-galN-acetyl groups were demonstrated on endothelium. In this respect, cerebral endothelium differs from noncerebral endothelium which is reported to have peanut agglutinin binding sites without neuraminidase pretreatment. Anionic groups on cerebral endothelium were demonstrated at the same locations as the lectin binding sites. Following neuraminidase pretreatment there was reduction, but not absence, of CF binding supporting the observation that surface charge is not wholly due to sialyl groups. The role of monosaccharide residues in states of altered cerebrovascular permeability remains to be determined.

Animals↗
PubMed1994

Arterial contractions induced by cumulative addition of calcium in hypertensive and normotensive rats: influence of endothelium.

Responses to cumulative addition of Ca2+ (0.2-2.5 mM) after precontraction with potassium chloride (KCl) and noradrenaline in Ca(2+)-free medium were studied in isolated mesenteric arterial rings from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). The Ca2+ contractions in 125 mM KCl-stimulated endothelium-denuded rings in the presence of atenolol (10 microM) and phentolamine (10 microM) were less marked in SHR than WKY, although the contractions to high concentrations of KCl in normal organ bath Ca2+ (1.6 mM) were similar in these strains. The difference in Ca2+ contractions between SHR and WKY during KCl stimulation was also present after 10-min pretreatment with 1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) in Ca(2+)-free medium. However, when noradrenaline (1 microM) was used as the agonist the Ca2+ contractions of endothelium-denuded rings in the two strains were comparable, while exposure to EGTA reduced these responses more effectively in SHR than WKY. Nifedipine (0.5 nM and 10 nM in KCl- and noradrenaline-stimulated rings, respectively) more efficiently inhibited the Ca2+ contractions in hypertensive than in normotensive rats. The presence of intact vascular endothelium attenuated the contractions to Ca2+ addition comparably (during KCl stimulation) or even more (during noradrenaline) in SHR when compared with WKY. NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) counteracted this attenuation correspondingly in WKY and SHR, and L-arginine (1 mM) restored it in both strains, whereas indomethacin (10 mM) was without effect on the response. However, mesenteric arterial relaxations induced by the endothelium-dependent agonists acetylcholine and ADP in noradrenaline-precontracted (1 microM) rings were clearly impaired in SHR, and also L-NAME (0.1 mM) reduced the responses to acetylcholine more efficiently in SHR. In contrast, the relaxations to acetylcholine and ADP in KCl-precontracted (60 mM) rings in the absence and presence of L-NAME were comparable between the two strains. In conclusion, attenuated contractile response to cumulative Ca2+ addition during stimulation with KCl clearly differentiated arterial smooth muscle of hypertensive and normotensive rats, suggesting altered function of cell membrane in SHR. The more pronounced effect of nifedipine on the response indicates abnormal function of voltage-dependent Ca2+ channels, and higher diminishing effect of EGTA on the contraction during noradrenaline suggests exaggerated action of the chelator on membrane-bound Ca2+ in SHR. Interestingly, the depressant effect of intact endothelium on the Ca2+ contraction response, mediated largely via nitric oxide, was not attenuated in SHR.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1994

Nonsteroidal antiinflammatory agents inhibit stimulated neutrophil adhesion to endothelium: adenosine dependent and independent mechanisms.

All nonsteroidal antiinflammatory drugs (NSAIDs) inhibit neutrophil aggregation (homotypic cell-cell adhesion) and do so without affecting expression of CD11b/CD18. Since the first step in acute inflammation is a critical interaction between neutrophils and the vascular endothelium (heterotypic cell-cell adhesion), we determined whether NSAIDs diminish the adherence of neutrophils to the endothelium. At antiinflammatory concentrations (0.5-5 mM) sodium salicylate, an NSAID that does not inhibit prostaglandin synthesis, inhibited stimulated but not unstimulated neutrophil adherence to endothelial cells (IC50 < 1 mM, P < 0.00001). Salicylates have previously been shown to inhibit oxidative phosphorylation and, predictably, sodium salicylate inhibited oxidative phosphorylation, as evidenced by depletion of ATP stores (875 +/- 75 pmol/10(6) PMN, [2.92 +/- 0.25 mM]) in stimulated (FMLP, 0.1 microM) but not resting neutrophils treated with antiinflammatory doses of sodium salicylate (EC50 = 1 mM, P < 0.00001). Indomethacin and piroxicam (10 and 30 microM) only minimally decreased ATP concentrations in stimulated and resting neutrophils. ATP is metabolized to adenosine, and we have previously demonstrated that both endogenously released (180-200 nM) and exogenous adenosine (IC50 = 250 nM) inhibit stimulated neutrophil adherence to endothelial cells. To determine whether the increased metabolism of ATP and the resultant increase in adenosine release were responsible for inhibition of neutrophil adhesion to endothelium, we determined whether addition of adenosine deaminase (ADA, 0.125 IU/ml), an enzyme that converts extracellular adenosine to its inactive metabolite, inosine, affected inhibition of neutrophil adhesion to endothelium by stimulated neutrophils. ADA significantly reversed inhibition of neutrophil adherence to endothelium by sodium salicylate (0.5-5 mM, P < 0.00001). This suggests that sodium salicylate inhibits neutrophil adherence by increasing adenosine release. Whereas indomethacin and piroxicam (10-50 microM) also inhibited stimulated neutrophil adherence to endothelial cells, ADA did not affect their inhibition of adherence. These studies demonstrate a heretofore unexpected antiinflammatory mechanism for salicylates: salicylates increase ATP hydrolysis and thereby enhance release of adenosine. Moreover, these data are consistent with the hypothesis that NSAIDs differ from one another with respect to their mechanisms of action.

Adenosine↗
PubMed1997

Effect of corticosteroids on healing of the corneal endothelium in cats.

BACKGROUND: Anterior segment surgery is frequently complicated by damage to the corneal endothelium. We examined the effects of corticosteroids, which are widely used for the suppression of postoperative inflammation, on the process of endothelial cell regeneration. METHODS: The effect of corticosteroids on healing of the corneal endothelium was examined in 10 domestic cats. In both eyes a circular area, 8 mm in diameter, was scraped off at the center of the corneal endothelium without damaging Descemet's membrane. Immediately after scraping, as well as 2 and 5 days later, each animal received a unilateral retrobulbar injection of betamethasone sodium phosphate (2 mg). The other eye served as a control and received a retrobulbar injection of the vehicle only. RESULTS: Evaluation of the corneal endothelium 2, 5 and 7 days after the trauma revealed that relative to the control contralateral eyes, the corticosteroid-treated eyes exhibited a higher mean coefficient of variation of the corneal endothelium cell area, fewer hexagonal cells, a larger number of polygonal cells with 3, 4 7 and 8 cellular facets, thinner corneas and less inflammation. CONCLUSIONS: These findings suggest that corticosteroids unfavorably affect the regeneration of corneal endothelial cells after injury. As corticosteroids appear to have both positive and adverse effects on corneal function after trauma, they should be used with caution.

Animals↗
PubMed1992

Saphenous vein endothelium-dependent relaxation in patients with peripheral vascular disease.

In vitro vasomotor responses of saphenous veins of 15 patients undergoing peripheral vascular bypass procedures were studied. Vessels were harvested by standard techniques, sectioned into 4 mm rings, and suspended in organ baths under isometric tension. Stimulation with cumulative doses of norepinephrine revealed a -logED50 of 6.85 +/- 0.12 M and maximal tension of 8.64 +/- 1.77 g. Patient characteristics suggesting high maximal response (by univariate analysis) included male sex (male 11.69 +/- 2.49 g versus female 5.08 +/- 1.69 g; p = 0.058). Intact and denuded rings were additionally tested for endothelium-dependent relaxation following submaximal norepinephrine precontraction. The vessels relaxed in response to acetylcholine (maximal relaxation 31.1 +/- 10.7% at 1 x 10(-6) M), calcium ionophore A23187 (85.3 +/- 11.8% at 1 x 10(-5) M), and sodium nitroprusside (150.8 +/- 15.2% at 1 x 10(-5) M), but only acetylcholine relaxation was completely endothelium-dependent. Calcium ionophore A23187 relaxation was partially dependent on the endothelium while sodium nitroprusside relaxation was entirely endothelium-independent. Negligible relaxation was observed in response to adenosine diphosphate (ADP) (12.1 +/- 12.8% at 1 x 10(-5) M) while histamine and serotonin caused additional contraction only. We concluded that, in patients undergoing vascular surgical procedures, the saphenous vein (1) demonstrates variable contractile function which appears to be greater in males following spinal anesthesia, and (2) exhibits moderate endothelium-dependent relaxation in response to acetylcholine and calcium ionophore A23187 but not to ADP, histamine, or serotonin.

Acetylcholine↗
PubMed1989

Benoxaprofen inhibits the adhesion of human monocytes to cultured vascular endothelium.

Pretreatment of human monocytes with benoxaprofen for at least 2 h produced a dose-dependent abrogation of their adhesion to monolayers of cultured porcine endothelium with 0.05 microgram/ml and 50.0 micrograms/ml of the drug inducing a mean 33% and 83% inhibition of adhesion respectively. When the endothelium was treated with the drug there was no modification of monocyte adhesion. In contrast, pretreatment of endothelium with 5.0 and 50.0 micrograms/ml benoxaprofen for at least 6 h resulted in a mean 35% and 31% inhibition of polymorphonuclear cell (PMN) adhesion in 6/11 experiments. This inhibitory effect was not seen when drug-treated PMNs were added to endothelium. An impairment of monocyte chemotactic migration was only apparent with high concentrations of the drug (50 micrograms/ml). These results suggest that an important anti-inflammatory property of benoxaprofen is the inhibition of monocyte adhesion to vascular endothelium.

Animals↗
PubMedDate not supplied

The influence of endothelium on the action of PGF2 alpha and some dihydropyridine-type calcium antagonists in porcine basilar arteries.

Vascular endothelium modulates the effect of various vasoconstricting mediators as well as the affinity of dihydropyridine-type calcium entry blockers. To further investigate this influence, vasoconstriction by PGF2 alpha as opposed to KCl and the affinity of nitrendipine and some related 3-ester side-chain derivatives were determined in isolated porcine basilar arteries in the presence and in the absence of intact endothelium, as well as in the presence of methylene blue. Treatment with methylene blue or mechanical endothelial damage increased the contractile work of basilar arteries stimulated by PGF2 alpha and reduced the affinity of the dihydropyridines in such precontracted vessels. Both experimental conditions resulted in nearly the same effect. In addition, the degree of intact endothelium, as determined by substance-P-induced vasodilation, significantly correlated with the corresponding efficacy of all dihydropyridines examined. In contrast, KCl-mediated contractions remained unchanged. It is suggested that the endothelium (probably due to the production and release of endothelium-derived vasorelaxing factors, such as EDRF and/or prostacyclin) may attenuate PGF2 alpha-induced transmembrane calcium influx through receptor operated calcium channels, whereas potential operated calcium channels seems to be unaffected.

Animals↗
PubMed1998

Endothelium-released adenosine triphosphate contributes to vasoconstrictor responses to periarterial nerve stimulation in isolated, perfused canine splenic arteries.

P2X-Purinoceptors and alpha1-adrenoceptors have previously been shown to be involved in double-peaked vasoconstrictor responses to periarterial electrical nerve stimulation in the isolated and perfused canine splenic artery. The present study was designed to investigate the influence of endothelium removal on vasoconstrictor responses to periarterial nerve stimulation, tyramine, noradrenaline, and adenosine triphosphate (ATP) in the isolated canine splenic artery. Intraluminal administration of saponin completely abolished the acetylcholine-induced vasodilatation and potentiated the vasoconstrictor response to KCl. Double-peaked vasoconstriction (two phases of vasoconstriction) was readily induced by periarterial electrical nerve stimulation in the canine splenic arterial preparation with or without endothelium and was consistently abolished by treatment with tetrodotoxin. Removal of endothelium slightly but significantly decreased the first-phase vasoconstrictor responses to stimulation of 1 or 10 Hz, and did not affect the second-phase. The vasoconstrictor responses to tyramine, noradrenaline, and ATP were not modified by endothelium removal. From these results, it is postulated that ATP released from endothelium, as a modulator of sympathetic nerve cotransmission, may partially contribute to the purinergic constriction component in the canine splenic artery.

Adenosine Triphosphate↗
PubMed1999

Enhanced, unaltered and impaired nitric oxide-mediated endothelium-dependent relaxation in experimental diabetes mellitus: importance of disease duration.

Long-term diabetes mellitus is characterized by impaired endothelium-dependent relaxation. In contrast, there is limited information on endothelial function in the early stages of the disease. In this study, we evaluated endothelial function ex vivo at early, intermediate and later stages of streptozotocin (STZ)-induced diabetes mellitus. We also evaluated the contribution of various endothelium-derived vasoactive factors at these stages of disease. In aortic rings contracted with norepinephrine, endothelium-dependent relaxation to acetylcholine was increased at 24 h following injection with streptozotocin compared with controls, normal after 1 and 2 weeks of disease or impaired at 8 weeks of disease. Endothelium-independent relaxation to nitroglycerin was unaltered at all stages. The enhanced relaxation at 24 h was mimicked in rings from alloxan-induced diabetic rats. Acute exposure of normal rings to streptozotocin in vitro caused no perturbation in acetylcholine-stimulated relaxation. Enhanced relaxation in diabetic rings at 24 h persisted in the presence of either indomethacin or tetraethylammonium. Acetylcholine-induced relaxation was blocked in both control and diabetic rings using L-nitroarginine but not by aminoguanidine. This suggests that the increased response was mediated by enhanced constitutive nitric oxide (NO). These studies show a triphasic response of increased, unaltered and impaired endothelium-dependent relaxation within the same model but dependent on the duration of disease. These studies could reconcile previous conflicting data in the literature and account for the observations of increases in tissue blood flow seen in early stages of experimental and human diabetes mellitus.

Acetylcholine↗
PubMed2002

Mechanisms underlying endothelium-dependent, nitric oxide- and prostanoid-independent relaxation in monkey and dog coronary arteries.

We compared the mechanisms of vasorelaxation of acetylcholine and of substance P with reference to K(+) channels, and analyzed pharmacologically the nature of endothelium-derived substance(s) other than NO and prostanoids in monkey and dog coronary arteries. Coronary arteries were isolated from monkeys and dogs, and the isometric tension of the artery strips was measured. In canine coronary artery strips treated with indomethacin plus N(G)-nitro- L-arginine ( L-NA) and partially contracted with prostaglandin F(2alpha), acetylcholine induced concentration-related relaxation, which was abolished by removal of the endothelium. The relaxation was markedly suppressed but not abolished in the strips exposed to high K(+) media. Charybdotoxin plus apamin potently inhibited the relaxation to the similar extent to that by high K(+) media, whereas glibenclamide or iberiotoxin had no effect. The relaxation was markedly inhibited by quinacrine, a phospholipase A(2) inhibitor, and ketoconazole, a selective cytochrome P450 (CYP) 3A inhibitor, but not by sulfaphenazole, a selective CYP 2C inhibitor. In contrast to acetylcholine, endothelium-dependent and indomethacin-plus- L-NA-resistant relaxation induced by substance P was not inhibited by high K(+) media, charybdotoxin plus apamin, or ketoconazole. Quinacrine and AA861, a 5-lipoxygenase inhibitor, inhibited the relaxation induced by substance P. In monkey coronary artery, acetylcholine-induced relaxation resistant to indomethacin plus L-NA was abolished by endothelial denudation and by treatment with high K(+) media, charybdotoxin plus apamin, progesterone and ketoconazole, but was not affected by iberiotoxin or sulfaphenazole. Substance P did not relax monkey coronary arteries. It is concluded that endothelium-dependent, nitric oxide- and prostanoid-independent relaxation induced by acetylcholine in monkey and dog coronary arteries are mediated by charybdotoxin plus apamin-sensitive but iberiotoxin-insensitive Ca(2+)-activated K(+) channel opening substance(s), which may be CYP3A-derived arachidonic acid metabolite(s). Contrasting to the response to acetylcholine, endothelium-dependent, indomethacin-plus- L-NA-resistant relaxation induced by substance P in dog coronary artery is not associated with K(+) channel opening, and may be mediated by 5-lipoxygenase product(s).

Acetylcholine↗
PubMed2005

Superoxide production and oxygen consumption in endothelium-intact and -denuded artery stimulated by angiotensin II.

Arteries stimulated by angiotensin II (AII) to contract do not display the expected augmentation of O2 consumption seen with other cardiovascular contractile agonists. We tested the hypothesis that superoxide (O2-) or other reactive oxidant species generated by AII played a role in the paradoxical O2 consumption response in porcine carotid artery, with or without an intact endothelium. Endothelium-denuded arteries were incubated with either 1 microM diphenylene iodonium (DPI), an inhibitor of NAD(P)H oxidase, 300 u/ml superoxide dismutase (SOD), a scavenger of O2-, or 20 U/ml catalase, an enzyme which promotes conversion of O2- (scavenged in the form of H2O2) to O2. DPI treatment resulted in the expected increase in O2 consumption upon contractile activation with AII challenge (1.05+/- 0.23 micromol/g/min; n = 6, p < .01), as did treatment with SOD (0.67+/- 0.20 micromol/g/min; n = 4, p < .05). Catalase incubation resulted in a burst of O2 generation upon AII challenge (1.30 +/- 0.21 micromol/g/min; n = 10, p < .001). In endothelium-intact arteries, O2 consumption was again not augmented with AII challenge; instead, a burst of O2 production was observed (0.66 +/- 0.22 micromol/g/min; n = 9, p < .05), which was not affected further by addition of catalase. Thus, the absence of apparent augmentation of O2 consumption during contractile activation of endothelium-denuded arteries was attributed to simultaneous NAD(P)H oxidase-dependent production of O2-, and attendant H2O2 and O2 generation which either and masked the detection of O2 consumed or suppressed mitochondrial uptake of O2, or both. An intact endothelium was required to manifest the burst of O2 generation with AII stimulation under normal conditions.

Angiotensin II↗
PubMed1991

Biology of the impaired endothelium.

The endothelium is a regulatory organ that mediates hemostasis, contractility, cellular proliferation, and inflammatory mechanisms in the vessel wall. Injury to the endothelium from hypertension, smoking, hyperlipidemia, and diabetes mellitus disrupts normal regulatory properties and results in abnormal endothelial cell function. Clinically, endothelial cell dysfunction can be manifested as vasospasm, thrombus formation, atherosclerosis, or restenosis. The normal hemostatic properties of the endothelium include the maintenance of a nonadhesive luminal surface, antithrombotic properties, anticoagulant properties, and fibrinolytic properties. The endothelial cell regulates smooth muscle cell contractility by the production of relaxing and constricting factors in response to physiologic stimuli. Endothelial cell injury is also an initial event in the development of atherosclerosis and restenosis by facilitating platelet adhesion and aggregation and by signaling the release of mitogens from platelets, macrophages, and endothelial cells, which stimulate smooth muscle cell proliferation. In addition, endothelial cells undergo morphologic and functional alterations in response to cytokine signals, which may contribute to the pathogenesis of vasculitis and atherosclerosis. In sum, the normal endothelium performs many regulatory functions which become altered when the endothelium is injured.

Animals↗
PubMed1988

Insulin, insulin-like growth factors, and vascular endothelium.

Endothelial cells form the intimal lining of the entire vascular system. The vascular endothelium is continuously and directly bathed by components of the bloodstream and represents the initial fixed anatomical surface with which these components come in contact. In the past decade, the methodologies for studying endothelial cell functions have markedly advanced, enabling direct and detailed study of the vascular endothelium. From such studies, it is now apparent that the vascular endothelium represents an extraordinarily complex network of cells demonstrating a multitude of distinct anatomic, metabolic, and immunologic properties critical to such processes as angiogenesis, atherosclerosis, thrombosis, neoplasia, and a variety of metabolic disorders including homocystinuria and diabetes mellitus. This report will focus on the interactions of insulin and the insulin-like growth factors (IGFs) with vascular endothelium, based on studies with cultured endothelial cells, isolated microvessels, and perfused organ systems. Data will be presented relevant to the following concepts: (1) endothelial cells, in culture and in vivo, have specific receptors for insulin, IGF-I, and IGF-II; (2) insulin, IGF-I, and IGF-II have both distinct and overlapping functions in cultured endothelial cells; (3) cultured endothelial cells process receptor-bound insulin, IGF-I, and IGF-II, by distinct processes; (4) in vivo, capillary endothelial receptors are integrally involved in the transport of intact insulin to subendothelial sites of insulin action; and (5) vascular endothelium has specialized cellular features that are likely to contribute to the unique interactions of endothelial cells with insulin and the IGFs.

Animals↗
PubMed1994

Endothelium-dependent relaxation of human resistance arteries in pregnancy.

OBJECTIVE: Reduced peripheral vascular resistance is an integral component of vascular adaptation in pregnancy. The precise mediators of the reduced resistance are unknown, however, and are often assessed by indirect means. In this study we investigated endothelium-dependent relaxation directly by examining acetylcholine-mediated relaxation in small arteries dissected from the subcutaneous fat layer undergoing biopsy at the time of gynecologic surgery and cesarean section. STUDY DESIGN: By means of a small vessel myograph we measured tension in resistance arteries of normal pregnant (n = 22) and nonpregnant (n = 10) women and assessed the contributions of vasodilatory prostanoids and endothelium-derived relaxing factor on endothelium-dependent relaxation, as elicited by acetylcholine (1 nmol/L to 10 mumol/L) after precontraction with 3 mumol/L norepinephrine. RESULTS: Endothelium-dependent relaxation was similar in arteries of pregnant and nonpregnant women. Sodium nitroprusside-induced relaxation was similar in arteries of pregnant and nonpregnant women. CONCLUSION: This study fails to demonstrate any increase in acetylcholine-induced endothelium-dependent relaxation in small subcutaneous arteries in pregnancy.

Acetylcholine↗
PubMed1990

Lysophosphatidylcholine: essential role in the inhibition of endothelium-dependent vasorelaxation by oxidized low density lipoprotein.

Endothelial cells are known to play an important role in the regulation of vascular tone. Here we demonstrate that modified low density lipoprotein (LDL) with copper oxidation or phospholipase A2 treatment elicits a potent inhibitory action on endothelium-dependent relaxations evoked by acetylcholine, although native LDL does not affect endothelium-dependent relaxations. Phosphatidylcholine of native LDL is converted to lysophosphatidylcholine during these modifications. Furthermore, lysophosphatidylcholine fraction separated from oxidized LDL (0.5mg.protein/ml) by thin layer chromatography abolished endothelium-dependent relaxations, although the remaining lipid fraction had little effects on endothelium-dependent relaxations. These results indicate that lysophosphatidylcholine is the principal substance for the impairment of endothelium-dependent relaxations by oxidized LDL and phospholipase A2 treated LDL.

Acetylcholine↗
PubMed1992

NG-hydroxy-L-arginine and hydroxyguanidine potentiate the biological activity of endothelium-derived relaxing factor released from the rabbit aorta.

We investigated the effects of NG-hydroxy-L-arginine (L-HOArg) and hydroxyguanidine (HOG) on the synthesis and vasorelaxant activity of endothelium-derived relaxing factor (NO) released from the rabbit aortic endothelium. Both L-HOArg (10 microM) and HOG (10 microM) equally potentiated the vasorelaxant activity of NO released by Ach (0.1 or 0.3 microM) from the luminally perfused rabbit aorta and bioassayed using the superfused strips of the endothelium-denuded rabbit aorta. This potentiation was caused by the generation of a more stable vasodilator during the chemical reaction of L-HOArg or HOG with NO and it was abolished by NG-nitro-L-arginine methyl ester (L-NO2Arg, 10 microM). In contrast, in organ baths, L-HOArg (10 microM) or HOG (10 microM) did not affect the relaxations of intact rabbit aortic rings induced by Ach (0.01-1 microM). At concentrations higher than 10 microM, both L-HOArg and HOG were endothelium-independent vasorelaxants. However, L-HOArg (100 microM) prevented the inhibition by L-NO2Arg (10 microM) of Ach-induced relaxations of bathed aortic rings which indicates that L-HOArg is still a substrate for the NO synthase in the endothelium of the rabbit aorta.

Acetylcholine↗