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At least 1,153 records · Page 64Linked to original sources
PubMed1990

Retention of endothelium-dependent vasodilatory responses in canine coronary arteries following cryopreservation.

In the present study, the cryoprotective effect of dimethyl sulfoxide (Me2SO) and fetal calf serum (FCS) on coronary endothelium and endothelium-dependent relaxation (EDR) responses was studied in isolated canine coronary arteries following cryostorage at -75 degrees C. Compared to the freshly isolated coronary arteries, the EDR responses to acetylcholine, thrombin, and calcium ionophore were not significantly altered following 1 day storage at -75 degrees C in the presence of 1.8 M Me2SO and 20% FCS. Prolonged cold storage to 7 days, however, resulted in a slight, but significant, rightward shift of the concentration-response curves of acetylcholine and thrombin, but not calcium ionophore. The maximum relaxant response after 7-day cryostorage was 80 to 85% of fresh controls. Omission of FCS from the cryostorage incubation medium further accentuated the loss of EDR responses to all three endothelium-dependent vasodilators tested. Scanning electron microscopic examinations of the intimal surface of the Me2SO and FCS cryostored canine coronary arteries confirmed the preservation of intimal endothelial cells following 1 or 7 days of storage at -75 degrees C, while significant patches of loss of endothelial cells were observed in the arteries cryostored only in the presence of Me2SO. No significant inhibitory effect of cryostorage was observed for the direct, endothelium-independent relaxation induced by isoproterenol, regardless of the presence or absence of FCS. These results demonstrate that slow freezing of canine coronary arteries to -75 degrees C in Krebs-Henseleit solution containing Me2SO and FCS provides good preservation of the vascular smooth muscle function and endothelium-dependent vasodilatory responses.

Animals↗
PubMed1985

Effects of peptides and non-peptides on isolated arterial smooth muscles: role of endothelium.

Peptides and non-peptides acting as vasoconstrictors or vasodilators have been tested in dog isolated carotid arteries with and without endothelium and in the presence and absence of a variety of antagonists and inhibitors of endogenous substances. It has been found that substance P and several other tachykinins, bradykinin, neurotensin, bombesin and acetylcholine relax the isolated artery only when the endothelium is present, while VIP, isopropylnoradrenaline, adenosine, histamine, prostaglandins E1 and E2, glucagon and insulin relax and angiotensin, vasopressin, oxytocin, 5-HT and noradrenaline contract the isolated vessel, no matter whether the endothelium is present or not. Peptide and non-peptide antagonists have been used with success to show that vasoconstrictors and vasodilators act on specific receptors, since their effects are reduced in the presence of antagonists, specific for one or another of the various agents. Inhibitors of the arachidonic acid cascade only reduce the effect of acetylcholine, suggesting that at least two different mechanisms are involved in the endothelium-mediated relaxation of arterial smooth muscles to peptide and non-peptide agents. The results summarised in this paper suggest that the site of action of several vasodilators is the endothelium, while other vasodilators and all the vasoconstrictors influence the arterial vessels tone presumably by acting on the smooth muscle cells.

Animals↗
PubMed1987

Endothelium enhances tachyphylaxis to angiotensins II and III in rat aorta.

Development of tachyphylaxis to angiotensin-induced contraction was compared in rings of rat aorta with and without functional endothelium. Rat aorta with functional endothelium rapidly developed marked tachyphylaxis to contraction induced by angiotensin II or angiotensin III. Destruction of endothelium significantly depressed, but did not prevent, development of tachyphylaxis to contractile responses induced by repeated exposure to angiotensin II or angiotensin III. The findings suggest that two mechanisms are involved in the development of tachyphylaxis to angiotensin in rat aorta, an endothelium-dependent mechanism and an endothelium-independent mechanism.

Angiotensin II↗
PubMed1991

Endothelium-dependent effects of pentoxifylline in rat aorta.

Experiments were performed with isolated rat aortas to study the vasoactive properties of pentoxifylline, a cyclic AMP phosphodiesterase inhibitor, which is used as a hemorheologic agent in the treatment of peripheral vascular disease. In rings precontracted with phenylephrine (0.1 microM), pentoxifylline (10 nM-10 microM) induced concentration-dependent relaxations which were not modified after incubation with indomethacin (3 microM) but which were almost completely abolished after incubation with methylene blue (10 microM) or after mechanical removal of the endothelium. After incubation with pentoxifylline (10 microM) for 30 min, the concentration-response curves for endothelium-dependent relaxations to acetylcholine were shifted to the left and the serotonin-induced contractions were decreased, while the relaxations to forskolin, which are endothelium-independent and cyclic AMP-mediated, were not altered. We conclude that pentoxifylline exerts vasoactive effects that are mediated by endothelium-derived relaxing factor (EDRF), and that pentoxifylline has negligible endothelium-independent vasodilating properties. These properties of inducing or potentiating EDRF-mediated effects might contribute to the efficacy of pentoxifylline in the treatment of vascular disease.

Acetylcholine↗
PubMed1994

Isoprenaline induces endothelium-independent relaxation and accumulation of cyclic nucleotides in the rat aorta.

The role of endothelium in isoprenaline-induced relaxation was investigated in aortic rings brought to different levels of pre-contraction. Relaxation elicited by isoprenaline decreased with increasing pre-contraction. However, relaxation was identical in rings with and without endothelium brought to the same initial tension by adjusting the noradrenaline concentration. Furthermore, isoprenaline increased cAMP and cGMP contents to the same levels whether endothelium was present or not. These results do not support an obligatory role for the endothelium in isoprenaline-induced relaxation in rat aorta. They indicate that relaxation induced by isoprenaline can be enhanced by the endothelium as a consequence of its effect on the precontraction level of the aorta.

Acetylcholine↗
PubMed1994

Influence of endothelium on Mg(2+)-induced relaxation in noradrenaline-contracted aorta from DOCA-salt hypertensive rat.

The aim of this study was to examine the influence of vascular endothelium on the relaxation induced by increased extracellular Mg2+ concentrations on isolated and noradrenaline-precontracted aorta from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and normotensive rats. In Mg(2+)-free physiologic salt solution (PSS), addition of Mg2+ (0.1-6.0 nM) caused concentration-dependent relaxation of noradrenaline-precontracted aorta with intact or disrupted endothelium. Mg(2+)-induced relaxation in intact aorta, however, was less in DOCA-salt hypertensive rats than in normotensive rats. When endothelium was disrupted, Mg(2+)-induced relaxation was depressed in aorta from both DOCA-salt hypertensive and normotensive rats. The same observations were made in presence of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor nitric oxide (EDRF/NO) biosynthesis. Mg(2+)-induced relaxation following contraction with noradrenaline was significantly less in intact aorta treated with L-NAME from DOCA-salt hypertensive rats than in intact aorta from normotensive rats. Indomethacin did not affect Mg(2+)-induced relaxation in intact aorta from normotensive rats whereas indomethacin significantly increased it in DOCA-salt hypertensive rats. It is concluded that (1) Mg(2+)-induced relaxation can be mediated by endothelium-dependent mechanisms implicating EDRF/NO; (2) the influence of EDRF/NO is more pronounced on the impaired Mg(2+)-induced relaxation of aorta from DOCA-salt hypertensive rats; (3) Mg(2+)-induced relaxation seems masked by vasoconstrictor prostaglandin release in DOCA-salt hypertensive rats; (4) these differences between normotensive and hypertensive rats could be related to the impaired endothelial function in aorta from DOCA-salt hypertensive rats.

Animals↗
PubMed1990

Proteoglycan synthesis by cultured liver endothelium: the role of membrane-associated heparan sulfate in transferrin binding.

Liver endothelium has been reported to possess membrane receptors for the iron-binding protein transferrin (Tf). Similarly, the core protein of proteoglycans (PG) associated with cell membrane in many cell systems can bind Tf. To find out if membrane-associated proteoglycans can explain Tf-binding ability of liver endothelium, we investigated the synthesis and distribution of proteoglycans by isolated, cultured liver capillary endothelium. Cells were isolated and cultured for 48 h in sulfate-free medium and pulse-labeled with 35SO4. The relative distribution of 35SO4-labeled macromolecules, determined in the extracellular (EC), membrane-associated (MA), and intracellular (IC) pools, was respectively 74, 15, and 10%. Membrane-associated proteoglycan (MA-PG) was further purified by ion exchange and gel chromatography. Glycosaminoglycan (GAG) chain characterization indicated about 78% chondroitin sulfate, 7% dermatan sulfate, and about 14% heparan sulfate (HS). Similar GAG chain characterization was made for PG in the EC and IC pools. Transferrin-binding ability of MA-PG was studied by affinity column chromatography, using CNBr-activated sepharose bound to transferrin. About 15% of the labeled MA-PG was specifically bound to Tf-affinity column and could be eluted by excess soluble Tf. This proportion was similar to the proportion of HS in the total membrane-associated pool. Moreover, the eluted labeled material was susceptible to pretreatment with heparitinase, confirming its HS nature. We conclude that the transport capillary endothelium of the liver can synthesize HS proteoglycans which are membrane-associated and this MA-HS pool can bind transferrin. The finding may provide a molecular basis for transferrin binding to liver endothelium and may explain the subsequent transendothelial transport of iron-transferrin complexes into the liver.

Animals↗
PubMed1991

Role of the endothelium in acetylcholine-induced relaxation and spontaneous tone of bovine isolated retinal small arteries.

Acetylcholine induced a variable concentration-dependent relaxation of bovine isolated retinal small arteries contracted with PGF2 alpha. The acetylcholine-mediated relaxation was linearly related to the sodium nitroprusside-induced relaxation, suggesting that the endothelium is well preserved in the vessels and that the variable effect of acetylcholine is due to variations in the soluble guanylate-cyclase enzyme activity in the smooth muscle. The vessels became desensitized to acetylcholine by repeated exposures. L-arginine and indomethacin did not abolish the desensitization. The vessels also became desensitized to the direct smooth muscle relaxing effect of sodium nitroprusside, indicating that desensitization to the endothelium-dependent relaxation by acetylcholine is related primarily to the vascular smooth muscle cells. Atropine, methylene blue and removal of endothelium abolished the acetylcholine-induced relaxation completely, whereas indomethacin had no inhibitory action on the acetylcholine-induced relaxation, suggesting that acetylcholine mediates release of EDRF (nitric oxide: NO) through stimulation of muscarinic receptors. Methylene blue contracted endothelium intact retinal arteries but a spontaneous tone was not present in endothelial denuded arteries. This may indicate a basal release of both a contractile factor, e.g. endothelin, and a relaxing factor. NO, form the retinal endothelium. The results demonstrate that endothelial-derived factors may participate in normal as well as pathophysiological regulation of retinal vascular smooth muscle tone.

Acetylcholine↗
PubMed1991

Presence of non-selective type of endothelin receptor on vascular endothelium and its linkage to vasodilation.

We studied the role of non-selective type (ETB) of endothelin (ET) receptor in the vasculature, using a ligand specific to the ETB receptor, [Glu9]-sarafotoxin S6b ([Glu9]SRTb). Endothelium-containing rat thoracic aorta possessed specific binding sites for 125I-[Glu9]SRTb, which were almost eliminated by removal of the endothelium, while ET-3-specific binding sites were not detected in the endothelium-intact rat aorta. Only ETB receptor was detected in the membranes from the endothelium of porcine thoracic aorta. [Glu9]SRTb exerted only vasodilation in rat aortic ring. These findings indicate that ETB receptors are located on vascular endothelium and linked to vasodilation.

Animals↗
PubMedDate not supplied

The effect of hypercholesterolemia on aortic endothelium studied en face.

The aortic endothelium of rabbits fed a stock diet containing 1 or 2% cholesterol for intervals of 1 day to 21 weeks was compared with that of normal rabbits on a stock diet without cholesterol. The endothelium was examined en face using the Häutchen technique. The aortic endothelium of the experimental animals revealed an increase in stigmata and stomata, multinucleated giant cells and leukocytes particularly about sites of branching. These changes were also observed in the endothelium overlying lipid deposits but in addition, there was an increase in mitoses, an alteration in the orientation of endothelial cells and their nuclei, and a change in their argyrophilic staining properties. Closely related to the endothelium was an increasing number of foam cells which appeared to be derived from monocytic leukocytes.

Animals↗
PubMed1983

Seeding of Dacron vascular prostheses with endothelium of aortic origin.

Seeding of autologous venous endothelium on Dacron vascular prostheses in dogs results in endothelial coverage of the prosthetic flow surface 4-6 weeks after implantation. Canine aortic endothelium, in contrast, usually fails to completely cover an unseeded prosthesis by pannus ingrowth even over much longer periods. To see if the success of endothelial seeding stems from a difference in the ability of venous and aortic endothelium to grow on prosthetic surfaces, we seeded freshly harvested autologous aortic endothelium on Dacron velour infrarenal aortic prostheses in dogs. Six weeks after surgery these prostheses showed the features reported to be typical of seeded prostheses. Scanning electron micrographs showed a luminal lining of flat polygonal cells without fibrin or adherent formed blood elements, and light microscopy showed an underlying layer containing aligned spindle-shaped cells with elongated nuclei and cell-lined subluminal channels. Control prostheses were covered with fibrin and platelet-rich thrombi everywhere except for limited pannus ingrowth at anastomotic sites. The results suggest that the success of autologous endothelial seeding cannot be ascribed to inherent differences in properties such as mitotic capacity or fibrinolysis between venous and aortic endothelium. The formation of complete endothelial linings by seeding must instead result from a more favorable condition for endothelial cell growth created by the cell harvesting or seeding process itself.

Animals↗
PubMed1988

Endothelium-dependent contraction induced by nicotine in isolated canine basilar artery--possible involvement of a thromboxane A2 (TXA2) like substance.

The present experiments were undertaken to determine whether the response to nicotine in the isolated canine cerebral artery is endothelium-dependent. Changes in the tension of arterial strips were recorded isometrically. Removal of the endothelium was carried out by gentle rubbing, and confirmed by scanning electron microscopy. Rubbing procedure did not affect the contractile response of the strips to serotonin. Treatment of unrubbed strips with nicotine (10(-4)M) caused a transient contraction. This response was abolished by removal of endothelium and attenuated by hexamethonium (5 x 10(-6)M) and atropine (10(-6)M). The nicotine-induced contraction was attenuated also by aspirin (5 x 10(-5)M), a cyclooxygenase inhibitor, OKY-046 (5 x 10(-5)M), a thromboxane A2 (TXA2) synthetase inhibitor and ONO-3708 (5 x 10(-9)M), a TXA2 antagonist. These results indicate that the nicotine-induced contraction in canine cerebral artery is endothelium-dependent, and suggest that the endothelium-derived contracting factor (EDCF) in the nicotine-induced response is a TXA2-like substance.

Animals↗
PubMed1993

Age, endothelium and aortic reactivity to calcium in Wistar rat.

The influence of age from (9 to 72 weeks) was investigated on contractions elicited by calcium in Wistar rat aortic rings with and without endothelium. The arteries were either depolarized by KCl or exposed to Bay K 8644 and concentration-effect curves to cumulative additions of CaCl2 were constructed. Whether the endothelium was present or not, the potency of CaCl2 but not its maximal effect decreased with age. The same decrease in potency was obtained with Bay K 8644, in the presence of which the maximal contractions were increased at 72 weeks. In K+ depolarized arteries, nitrendipine (10(-10) and 10(-9) M) markedly decreased maximal contraction elicited by CaCl2 and it moderately displaced to the right the concentration-effect curves. The endothelium did not modify the responses to CaCl2 of depolarized arteries, in the absence of nitrendipine. However it markedly enhanced the depressor effect of nitrendipine in these preparations, and it impaired contractions elicited by calcium in the presence of Bay K 8644. These effects of the endothelium were both less at 72 weeks than at younger ages. These experiments show a possible impairment of the inhibitory effect of the endothelium in 72 week old rats in the presence of both agonist and antagonist dihydropyridines.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Endothelium-derived nitric oxide protection of spontaneous coronary contractions in the rabbit by countering Ca2+ influx via the voltage-sensitive Ca2+ channel.

The mechanism of spontaneous coronary contractions was investigated in the rabbit. Arteries with intact endothelium did not spontaneously contract. However, spontaneous coronary contractions were generated after the removal of the endothelium. NG-nitro-L-arginine methyl ester and methylene blue, the inhibitors of the formation and the action of nitric oxide, respectively, induced contractions in endothelium-intact arteries. Spontaneously produced contractions in endothelium-denuded arteries were reversibly inhibited by a Ca(2+)-free solution and by nifedipine, but not by inhibitors of neurotransmitters or prostanoids. These findings may indicate that spontaneous coronary contractions in the rabbit may be attributed to Ca2+ influx via the voltage-sensitive Ca2+ channel. The basal release of endothelium-derived nitric oxide may, in part, antagonize this Ca2+ influx.

Animals↗
PubMed1994

Gou-teng (from Uncaria rhynchophylla Miquel)-induced endothelium-dependent and -independent relaxations in the isolated rat aorta.

Gou-teng is a drug used for treatment of hypertension in Chinese medicine. Its antihypertensive action has been previously confirmed in the spontaneously hypertensive rat (SHR). Here, its vasorelaxing effect and the mechanisms of actions were studied in vitro. Gou-teng extract (GTE) relaxed the norepinephrine (NE)-precontracted aortic ring preparations isolated from Wistar Kyoto rats (WKY) with and without intact endothelium; the latter was significantly less sensitive than the former. The GTE-induced endothelium-dependent relaxation was significantly inhibited by NG-monomethyl-L-arginine (NMMA) in a dose-dependent manner while indomethacin did not affect the relaxation. Atropine inhibited the acetylcholine (ACh)-induced endothelium-dependent relaxation but did not the GTE-induced one. Furthermore, once GTE was applied, the following NE-induced contraction was significantly reduced even after repeated washout. NMMA effectively reduced and rather reversed this residual effect of GTE. From these results, it is concluded that GTE relaxes the NE-precontracted rat aorta through endothelium-dependent and, to lesser extent, -independent mechanisms. The endothelium-dependent component would be mediated by EDRF/NO pathway in which the muscarinic cholinoceptors were not involved. Thus, GTE appears to be a potent and long-lasting vasodilator mainly through EDRF/NO release.

Acetylcholine↗
PubMed1994

NG-nitro-L-arginine-resistant endothelium-dependent relaxation induced by acetylcholine in the rabbit renal artery.

Studies were designed to determine the extent of the involvement of endothelium-derived relaxing factor(s) other than nitric oxide (NO) in vascular relaxation in response to acetylcholine (ACh) in the rabbit renal artery. ACh (10(-9)-10(-6) M) induced concentration-dependent relaxation of isolated endothelium-intact arterial rings preconstricted with noradrenaline. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, partly inhibited the ACh-induced endothelium-dependent relaxation, whereas it almost completely abolished the production of cyclic-3', 5'-guanosine monophosphate (cGMP) in these rings in response to ACh. Methylene blue, an inhibitor of guanylate cyclase, had an essentially similar effect to L-NAME on the relaxation. Indomethacin, an inhibitor of cyclooxygenase, had no effect. High concentrations of potassium chloride (to inhibit endothelium-dependent hyperpolarization), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), a voltage-dependent or Ca(2+)-dependent K+ channel blocker, partly inhibited the relaxation while, in contrast, glibenclamide, an ATP-sensitive K+ channel blocker, had no effect. Ouabain, an inhibitor of Na+, K(+)-ATPase, also partly inhibited the ACh-induced relaxation, especially the higher concentration effect. Application of L-NAME together with ouabain, TEA, or a high concentration of potassium chloride completely abolished the relaxation. These results suggest that ACh-induced endothelium-dependent relaxation in the rabbit renal artery is mediated by NO, and by an other factor(s), which relaxes the vascular smooth muscle through opening K+ channels other than ATP-sensitive ones, and/or through the activation of a Na+, K(+)-pump.

Acetylcholine↗
PubMed1988

The influence of circulatory overload on extraalveolar microvessel endothelium of dog lung in vivo.

In an earlier study from this laboratory, morphometric evaluations of the alveolar capillary endothelium of the lungs of intact dogs were recorded after periods of sustained increases of pulmonary microvascular pressures (D. O. DeFouw, W. O. Cua, and F. P. Chinard, 1983, Microvasc. Res. 25, 56-67). In the present study ultrastructural characteristics of the extraalveolar microvessel endothelium of these dog lungs were evaluated. Small (25- to 50-microns luminal diameter) nonmuscular vessels, which adjoin the alveolar capillaries, and larger (51-200 microns) partially muscular and muscular microvessels were assessed. After increased microvascular filtration, to be expected from the increased hydrostatic pressures, fluid accumulation was found only in the connective tissue sleeves of the larger microvessels. The endothelium of these partially muscular and muscular vessels was markedly affected by fluid distension of the periendothelial interstitium. The endothelial response included the appearance of basal (abluminal) surface invaginations, de novo plasmalemmal vesicle formation, and increased numbers of cytoplasmic vacuoles. The small nonmuscular microvessels lacked both the fluid cuffs and the alterations of endothelial ultrastructure. This latter observation is consistent with the previous report from this laboratory that indicated an absence of both alveolar septal edema and increased capillary endothelial vesicle densities in these lungs (DeFouw et al., 1983). Thus, it seems likely that the conformational changes of the endothelium of the larger microvessels were related to the formation of the periendothelial fluid cuffs. The mechanisms responsible for this endothelial response have not been determined but can be explained on the basis of the testable hypothesis that they are secondary to an increase of tissue pressure associated with accumulation of tissue fluid. These changes may thus represent a secondary structural adaptation to the increased tissue pressures and may serve as a potential vesicular-vacuolar pathway across the endothelium.

Animals↗
PubMed1987

Uptake and inactivation of thrombin on the subendothelium: comparisons with endothelium.

One aspect of the non-thrombogenicity of endothelium is the property to bind and inhibit thrombin. Loss of the endothelial layer gives rise to a thrombogenic surface. The present study concerns uptake and inactivation of thrombin on endothelium as well as subendothelium. Both the immediate subendothelial layer and the media were investigated. Binding and inhibition of thrombin was assayed using both a synthetic chromogenic substrate and fibrinogen. In the latter case thrombin enzymatic activity was assessed by measuring liberation of fibrinopeptide A. There was a linear relationship between thrombin in the solution and thrombin enzymatic activity recovered on the surface on both endothelium and media. 30-50 per cent of the surface bound thrombin measured with the chromogenic substrate was also active towards fibrinogen. Preincubation of endothelium with plasma gave rise to an increased loss of thrombin from the solution at the same time as less thrombin was recovered on the surface. This indicates increased inactivation. Increased inactivation could also be obtained by pretreatment with antithrombin (AT) but not with AT-depleted plasma. The same general pattern was seen on the subendothelium but not on the media. It is concluded that inhibition of thrombin occurs on the endothelium and can be augmented by prior binding of AT to the surface. This effect although less pronounced can also be obtained on the subendothelium. The deeply injured vessel is much less capable of inhibiting thrombin.

Animals↗