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PubMed2000

Effects of penetrating keratoplasty rejection on the endothelium of the donor cornea and the recipient peripheral cornea.

PURPOSE: To determine the effects of penetrating keratoplasty rejection on the recipient endothelium. METHODS: Twenty transplanted corneas of 20 keratoconus patients were enrolled in this study. Ten of the corneas had undergone allograft rejection and the other 10 grafts had an uneventful postsurgical course. The endothelium of the donor cornea and the endothelium of the recipient peripheral cornea were evaluated by wide-field specular microscopy. RESULTS: The transplanted corneas that underwent allograft rejection showed a marked decrease in endothelial cell density not only in central donor cornea but also in the recipient peripheral cornea compared with that in the uneventful transplanted corneas. Additionally, the recipient endothelium had significant pleomorphism in the rejection group. There were no morphologic differences in the peripheral donor cornea between the control group and the rejection group. CONCLUSIONS: Our findings indicate that the recipient peripheral endothelium is also affected by allograft rejection, perhaps because of the contribution of recipient endothelium to the wound healing process after allograft rejection.

Adult↗
PubMed1997

Distribution of muscarinic receptors on the endothelium of cortical vessels in the rat brain.

Functional and pharmacological studies have suggested that there are muscarinic receptors (mAChRs) on the endothelial cells of major cerebral arteries, while recent immunological studies indicate that there are no mAChRs on the endothelium of brain capillaries. This difference may be because the distribution of mAChR on the endothelium varies with the type of vessel. This paper examines the distribution of mAChR on the vascular endothelium along intraparenchymal blood vessels in the rat brain by immunolabelling and laser confocal microscopy. Sections were immunostained by combinations of an anti-mAChR antibody (M35) with antibodies to endothelial (anti-GLUT1), or to smooth muscle markers (anti-actin). Antibody labellings were detected with fluorescent second antibodies. Most of the penetrating vessels bore mAChR immunolabelling which coincided over almost all the vessel surface with endothelial labelling. The mAChR immunolabelling was less widespread over the endothelium on the medium sized vessels (diameter < 50 microm) and only 50% of these vessels had mAChR staining on the endothelium. There was no mAChR immunostaining on the endothelium of the capillaries. In contrast with the basilar artery, there was no mAChR immunolabelling on the smooth muscle layer of the intracortical vessels. These data indicate that the intensity of mAChR immunolabelling decreases along the vascular tree from large conducting vessels to capillaries.

Actins↗
PubMed2003

Hyperthyroidism enhances endothelium-dependent relaxation in the rat renal artery.

OBJECTIVE: Hyperthyroidism has pronounced effects on vascular function and endothelium-dependent relaxation. The aim of the present study was to identify mechanisms underlying hyperthyroidism-induced alterations in endothelial function in rats. METHODS: Animals were subjected to either a single injection (36 h) or 8 weeks treatment with the thyroid hormone triiodothyronine (T3, i.p.). Vascular reactivity and agonist-induced hyperpolarization were studied in isolated renal arteries. Endothelial nitric oxide (NO) synthase expression and cyclic AMP accumulation were determined in aortic segments. RESULTS: Endothelium-dependent relaxations to acetylcholine (ACh) were enhanced by T3 36 h after injection and after treatment for 8 weeks. Thirty-six hours after T3 application, relaxation mediated by the endothelium-derived hyperpolarizing factor (EDHF) and by endothelium-derived NO were significantly enhanced. After 8 weeks treatment with T3, however, EDHF-mediated relaxation was impaired, whereas NO-mediated relaxation remained enhanced. KCl- and ACh-induced hyperpolarizations were more pronounced in arteries from rats treated with T3 for 36 h compared to control, whereas in arteries from rats treated with T3 for 8 weeks both responses were attenuated. In rats treated for 36 h, vascular cyclic AMP levels were enhanced in the aorta and inhibition of protein kinase A attenuated EDHF-mediated relaxations of the renal artery without affecting responses in arteries from the control group. In the aorta from rats treated with T3 for 8 weeks, the expression of the endothelial NO synthase was markedly up-regulated (463+/-68%). CONCLUSIONS: These data indicate that short-term treatment with T3 increases endothelium-dependent relaxation, most probably by increasing vascular cyclic AMP content. Following treatment with T3 for 8 weeks, expression of the endothelial NO synthase was enhanced. During this phase, NO appears to be the predominant endothelium-derived vasodilator.

Acetylcholine↗
PubMed1997

Perfusion-induced changes in cardiac contractility and oxygen consumption are not endothelium-dependent.

OBJECTIVE: Are substances released from rat coronary endothelial cells responsible for the increase in contractility and oxygen consumption (Gregg phenomenon) seen with an increase in cardiac perfusion? METHODS: In an isovolumically contracting, Langendorff, crystalloid perfused rat heart (n = 6) at 27 degrees C, coronary flow was changed (from 4.4 to 15.4 ml.min-1.gww(-1)) before and after the endothelium was made dysfunctional by Triton X-100. Vascular endothelium and smooth muscle function were tested with bradykinin (BK, 1 microM, an endothelium-dependent dilator) and papaverine (PAP, 1 microM, an endothelium-independent dilator) in a preconstricted vascular bed (vasopressin, VP, 3 nM). RESULTS: Before Triton X-100, coronary resistance (at constant flow) decreased significantly in response to BK and to PAP. After Triton X-100 treatment the dilatory response to BK was abolished while the PAP response was still present, suggesting endothelial dysfunction with intact smooth muscle function. Due to Triton X-100 treatment, coronary resistance increased significantly. Therefore coronary flow changes were also applied during a similar increase in coronary resistance induced by VP infusion (3 nM) before Triton X-100 treatment. During control, developed left ventricular pressure (dev Plv) increased with 68 +/- 21% and oxygen consumption (VO2) increased with 122 +/- 25% in response to the maximal increase in coronary flow. During increased coronary resistance with and without functional endothelium, dev Plv increased by 57 +/- 16 and 64 +/- 22%, respectively, and VO2 increased by 126 +/- 21 and 103 +/- 20%, respectively, in response to the maximal increase in flow. These changes were not significantly different from control. CONCLUSION: The results suggest that the arterial endothelium is not involved in the Gregg phenomenon.

Animals↗
PubMed1998

Impairment of endothelium-independent vasodilation in patients with hypercalcemia.

OBJECTIVE: Patients with primary hyperparathyroidism (PHPT) and/or hypercalcemia are at increased risk for myocardial ischemia. Whether PHPT is associated with altered endothelium-dependent dilation, vascular smooth muscle cell function, or both is unknown. This study was performed to test the hypothesis that endothelium-dependent, flow-mediated dilation (FMD) and/or endothelium-independent, nitroglycerin-induced dilation (NMD) is impaired in the preclinical phase of vascular disease in patients with PHPT. METHODS: Twenty-six PHPT patients (mean +/- SD; age 55 +/- 15 y, serum calcium 3.00 +/- 0.37 mmol/l, serum phosphate 0.79 +/- 0.21 mmol/l, iPTH 249 +/- 262 pg/ml) with no evidence of coronary artery disease (CAD) as well as 26 normocalcemic control subjects (CTL; age 51 +/- 12 y) were studied. FMD following reactive hyperemia and NMD after 0.8 mg nitroglycerin (NTG) were assessed in the brachial artery by using high resolution ultrasound (7 MHz). RESULTS: NMD was impaired in PHPT patients compared to CTL (11.9 +/- 3.9% vs. 15.6 +/- 5.7%; p = 0.012). FMD was similar in both study groups (11.6 +/- 4.6% vs. 12.6 +/- 4.9; NS). The ratio of FMD to NMD was significantly different between PHPT patients and CTL (0.98 +/- 0.19 vs 0.81 +/- 0.25, p = 0.0009). On multiple stepwise regression analysis serum calcium was independently associated with the FMD/NMD ratio (r = 0.34, p = 0.017). CONCLUSIONS: Endothelium-independent vasodilation is impaired in PHPT patients without clinical evidence of coronary artery disease compared to normocalcemic CTL, while endothelium-dependent dilation was similar in both study groups. Thus, altered arterial reactivity in the course of PHPT may predominantly involve the arterial media and not the endothelium as observed previously in patients with various stages of atherosclerosis.

Adult↗
PubMed1999

Lipids and the endothelium.

The normal endothelium is characterised by the production of a number of molecules which affect the contractile state of adjacent myocytes and the behavior of formed elements within the blood stream, and by the absence of cell surface adhesion molecules. In addition, endothelial cells are important modulators of coagulation and fibrinolysis. Whilst effects of lipids have been documented on many of these endothelial processes, there is particularly strong evidence for effects on the vasodilatation mediated by endothelium derived nitric oxide and on the interaction between leukocytes and the endothelial surface. Both LDL cholesterol and triglyceride rich lipoproteins impair endothelium dependent vasodilatation. The effects of LDL cholesterol are primarily evident for lipoprotein particles that have been oxidised with evidence for effects of specific constituents of oxidised LDL, such as lysophosphatidylcholine (LPC). LDL effects have been demonstrated at numerous sites of the nitric oxide signaling pathway including receptor-G protein coupling, nitric oxide synthase and NO bioactivity, with evidence for enhanced superoxide formation and the consequent production of the less potent dilator peroxynitrite. The effects of lipids on endothelium dependent vasodilatation can be reversed not only by reducing the level of elevated lipids levels but also by provision of the NOS substrate, L-arginine and by the provision of antioxidants, although the mechanism for these effects are not fully elucidated. The adhesion of leukocytes to the endothelial surface is stimulated by low density and triglyceride rich lipoproteins. As with endothelium dependent vasodilatation, the effects of LDL cholesterol are primarily evident for low-density lipoprotein particles that have been oxidised, and many of the effects of oxidised LDL can be mimicked by LPC. HDL can overcome pro-adhesive effects of oxidised LDL. The effects of LDL on leukocyte adhesion are secondary to the expression of adhesion molecules on the luminal surfaces of endothelial cells. In addition to the likely deleterious effects of lipids on endothelium-mediated vasodilatation and leukocyte-endothelial cell interaction, lipids have been shown to affect a number of other endothelial processes and function. Thus, oxidised LDL affects endothelial ET1 and PGI2 release. Although effects have been shown on endothelial cell growth and apoptosis and on endothelial processes related to thrombosis and fibrinolysis, these effects have been less extensively studied than endothelial dependent vasodilatation and leukocyte-endothelial cell interaction. Many of the effects of elevated or modified low density and TG rich lipoproteins on endothelial cells and endothelial cell processes could be expected to contribute to the development of atherosclerosis and therefore, to the association between lipids and atherosclerotic, particularly coronary, vascular disease. However, the extent to which "endothelial dysfunction" accounts for the known relationships between serum lipid concentrations and CHD is yet to be established.

Animals↗
PubMed2000

Time course of changes in endothelium-dependent and -independent relaxation of chronically diabetic aorta: role of reactive oxygen species.

In the present study, the role of reactive oxygen species and the contribution of antioxidant defence in the time course of changes in acetylcholine-stimulated endothelium-dependent and sodium nitroprusside-stimulated endothelium-independent relaxation were investigated in aortic rings isolated from 6-month streptozotocin-diabetic and age-matched control rats. Although there were no significant differences in the degree of the peak relaxations produced by a single administration of acetylcholine (1 microM) or sodium nitroprusside (0.01 microM) between control and diabetic rings, the endothelium-dependent and -independent relaxant responses were more transient and the time required to reach a peak relaxation after addition of acetylcholine was shorter in diabetic vessels. Pretreatment of diabetic vessels with superoxide dismutase (100 U/ml) normalized the recovery phases of endothelium-dependent and -independent relaxations, but had no effect on the peak responses to acetylcholine and sodium nitroprusside. In the presence of diethyldithiocarbamate (5 mM), an inhibitor of superoxide dismutase, the transient nature of the relaxant response to acetylcholine or sodium nitroprusside was more marked and the peak relaxations were inhibited; these effects of diethyldithiocarbamate were more pronounced in diabetic than in control rings. Catalase, 160 U/ml, decreased the peak relaxant response to acetylcholine and accelerated fading of the relaxation in diabetic aorta. Similar results were obtained for control aorta with a higher concentration of catalase (550 U/ml). Pretreatment with 3-amino-1,2,4 triazole (5 mM), a catalase inhibitor, inhibited the peak relaxant response to acetylcholine in diabetic rings. The combination of superoxide dismutase (100 U/ml) plus 3-amino-1,2,4 triazole (5 mM) produced an increase of the transient nature of endothelium-dependent relaxation of diabetic rings greater than that with 3-amino-1,2,4 triazole alone. Neither catalase nor 3-amino-1,2,4 triazole affected the characteristics of sodium nitroprusside-induced relaxation. Desferrioxamine, an inhibitor of hydroxyl radical (.OH) production, or mannitol, a.OH scavenger, had no effect on the characteristics of either acetylcholine- or sodium nitroprusside-induced relaxation in control and diabetic rings. Biochemical measurements revealed an inhibited superoxide dismutase activity in diabetic aorta together with activated catalase. Our findings suggest that, during the chronic phase of streptozotocin-diabetes, excess superoxide (O(2)(. -)) is responsible for the enhanced transient nature of endothelium-dependent and -independent relaxation of aorta via a reduction in bioavailable concentrations of nitric oxide (NO). However, the involvement of hydrogen peroxide (H(2)O(2)) in the establishment of acetylcholine-stimulated relaxation may be increased, which is likely to account for the maintenance of the relaxant effect of acetylcholine in chronically diabetic vessels.

Acetylcholine↗
PubMed2003

NS-398, a selective cyclooxygenase-2 blocker, acutely inhibits receptor-mediated contractions of rat aorta: role of endothelium.

NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl)-methane sulfonamide) is a selective inhibitor of the cyclooxygenase-2 isozyme in vitro and in vivo. This study reports on acute inhibition of receptor-mediated contractions of isolated rat aorta by NS-398 and its modulation by endothelium-derived nitric oxide. NS-398 (1-10 microM) blocked norepinephrine, and 5-hydroxytryptamine (5-HT) evoked contractions and suppressed E(max) responses for both agonists. E(max) changes occurred in endothelium-intact vessel rings and in the absence, as well as in the presence of cycloheximide or dexamethasone in the physiological salt solution (PSS) bathing the tissues. NS-398 altered contractions to these receptor agonists in denuded rings only at 10 microM, and did not significantly alter contractions to KCl and sodium fluoride in all situations. NS-398 (3 and 10 microM) reduced aortic contractions initiated by cyclopiazonic acid (CPA), a sarcoplasmic reticulum Ca(2+)-ATPase blocker, in endothelium intact rings bathed with PSS with/without nitro-D-arginine methyl ester (D-NAME; 100 microM), but did not alter contractions to the compound in endothelium-denuded aortic rings and in vessel rings bathed with PSS+L-NAME (100 microM). Western blot analyses reveal significantly denser cyclooxygenase-2 protein expressions in freshly isolated endothelium-intact, compared to, denuded vessel segments. We conclude that: (1) cyclooxygenase-2 is constitutively expressed in rat aortic endothelial and smooth muscle cells, and (2) NS-398 modulates aortic contractions principally through an action on endothelial cyclooxygenase-2. Our data strongly suggest that cyclooxygenase-2 and/or its product(s), in concert with endothelium-derived nitric oxide, regulates the sarcoplasmic reticulum Ca(2+) pump activity in rat aorta.

Animals↗
PubMed2003

An endothelium-derived factor modulates purinergic neurotransmission to mesenteric arterial smooth muscle of hamster.

The interaction between the endothelium and purinergic perivascular nerves was investigated by measuring the changes in amplitude of excitatory junction potential (EJP) of smooth muscle cells in hamster mesenteric arteries (100-350 microm). Uridin-5'-triphosphate (UTP) (100 microM) applied to endothelium-intact preparations evoked a hyperpolarization of 17.0 +/- 0.7 mV (n=46). During this hyperpolarization, the amplitude of electrically evoked EJPs was inhibited to about 50% of that of the control. In endothelium-denuded preparations, UTP (100 microM) neither hyperpolarized the smooth muscle nor inhibited the amplitude of the EJP. Neither a nitric oxide (NO) synthase inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME) (100 microM), nor a cyclooxygenase inhibitor, indomethacin (1 microM), had an effect on the UTP-evoked hyperpolarization and inhibition of the electrically evoked EJP. The UTP-evoked membrane hyperpolarization and inhibition of the EJP amplitude was antagonized by the P2Y receptor antagonist, cibacron blue (100 microM). Endothelium-derived hyperpolarizing factor (EDHF)-mediated hyperpolarization was inhibited by either adventitial or intimal application of apamin (0.1 micro and charybdotoxin (0.1 microM). However, the EJP inhibition was still present. In apamin- and charybdotoxin-treated preparations, focal application of adenosine 5'-triphosphate (ATP) (10 mM) evoked a depolarization of 15.5 +/- 1.3 mV (n=15). This postjunctional response was not modified by UTP (15.3 +/- 1.7 mV, n=4, P>0.05). These results suggest that exogenously applied UTP activates P2Y receptors of endothelium to release endothelium-derived factors, which in turn inhibit ATP release from purinergic nerves.

4-Aminopyridine↗
PubMed1998

Involvement of endothelium in relaxant action of glibenclamide on the rat mesenteric artery.

The present report describes the complex effect of glibenclamide, an antidiabetic sulfonylurea agent, on the rat isolated mesenteric artery. Although glibenclamide concentration dependently reversed the relaxant effect of pinacidil, an activator of ATP-sensitive K+ channels (the concentration for half-maximum reversal effect was 0.56 microM with endothelium and 0.17 microM without endothelium), in the artery precontracted with phenylephrine (1 microM), it relaxed phenylephrine-induced sustained contraction at higher concentrations (IC50: 4.4+/-1.1 microM with endothelium and 226.1+/-44.2 microM without endothelium). The relaxant effect of glibenclamide was partially inhibited by pretreatment of the artery with either NG-nitro-L-arginine (10-100 microM) or methylene blue (1 microM). Indomethacin (10 microM) had no effect. Moreover, glibenclamide also concentration dependently (3-500 microM) reduced the sustained contraction induced by 60 mM K+ (IC50: 99.5+/-16.1 microM). The relaxation induced by glibenclamide was not affected by various putative K+ channel blockers such as charybdotoxin (100 nM), tetraethylammonium ions (1 mM), apamin (100 nM) and 4-aminopyridine (1 mM). The results indicate an involvement of the endothelium, probably of nitric oxide, in the relaxation induced by glibenclamide in the endothelium-intact rat mesenteric arteries. The inhibitory effect of glibenclamide on the high-K+-induced contraction suggests that glibenclamide may interfere with Ca2+ influx, which in turn affects intracellular Ca2+ levels in arterial smooth muscle, leading to reduction of muscle contractility. It is suggested that two distinct pharmacological effects induced by glibenclamide may be mediated through different glibenclamide binding sites, however, the data show an overlap of concentrations of glibenclamide for producing the two effects in rat isolated mesenteric arteries.

Animals↗
PubMed1999

Endothelium-dependent contraction and direct relaxation induced by baicalein in rat mesenteric artery.

The vascular effect of purified baicalein from Scutellaria baicalensis Georgi (Huangqin) was examined in rat isolated mesenteric arteries. Baicalein exerts both contractile and relaxant effects on the U46619-, phenylephrine- or high K+-contracted endothelium-intact arteries. In endothelium-denuded arteries, the contractile response to baicalein (0.3-10 microM) was absent while the relaxant response to baicalein (30-300 microM) remained. Pretreatment with 100 microM N(G)-nitro-L-arginine (L-NNA) or 3 microM methylene blue abolished the baicalein-induced contraction while 10 microM indomethacin or 100 nM BQ610 had no effect. Pretreatment with baicalein (3-10 microM) significantly attenuated the relaxation induced by acetylcholine or by A23187. In contrast, baicalein did not affect the sodium nitroprusside-induced relaxation in endothelium-denuded arteries. Baicalein also concentration dependently inhibited the contractile response to 1 microM phorbol 12,13-diacetate (PDA) in Ca2+-free solution. Baicalein had little effect on the contractile response to 60 mM K+ or to 10 mM caffeine in endothelium-denuded arteries. The baicalein-induced relaxation was unaffected by 1 microM glibenclamide or by 3 mM tetraethylammonium ions in endothelium-denuded arteries. These results indicate that baicalein at low concentrations caused a contractile response and inhibited the endothelium-dependent relaxation, probably through inhibition of endothelial nitric oxide (NO) formation/release. At higher concentrations, baicalein relaxed the arterial smooth muscle partially through inhibition of the protein kinase C-mediated contractile mechanism.

Animals↗
PubMed1995

Endothelium-dependent contraction of canine coronary artery is enhanced by crystalloid cardioplegic solution.

Experiments were designed to determine whether hyperkalemic crystalloid cardioplegic solution enhances endothelium-dependent contraction of coronary arteries. Segments of canine coronary arteries (n = 8 in each group) were preserved in cold (4 degrees C) crystalloid cardioplegic solution (group 1) and physiologic solution (group 2) for 60 minutes. Segments of preserved and control (group 3) coronary arteries with or without endothelium were suspended in organ chambers to measure isometric force. Perfusate hypoxia (oxygen tension 35 +/- 5 mm Hg) caused endothelium-dependent contraction in the arteries of all three groups. However, vascular segments with endothelium of group 1 exhibited hypoxic contraction (68.5% +/- 15.3% of the initial tension contracted by prostaglandin F2 alpha 2 x 10(-6) mol/L, p < 0.05) that was significantly greater than contraction of the group 2 and group 3 segments with endothelium (26.6% +/- 5.6% and 20.6 +/- 4.4%). The hypoxic contraction in arteries of group 1 could be attenuated by NG-monomethyl-L-arginine, the blocker of endothelial cell synthesis of the nitric oxide from L-arginine. The action of NG-monomethyl-L-arginine could be reversed by L-arginine but not D-arginine. Thus after preservation with cardioplegic solution, augmented endothelium-dependent contraction, occurs by L-arginine-dependent pathway, would favor coronary vasospasm after cardiac operation.

Animals↗
PubMed1996

Preservation of endothelium-dependent vasodilation with low-potassium University of Wisconsin solution.

University of Wisconsin solution has provided excellent myocardial preservation. However, the high potassium content of the currently available University of Wisconsin solution has been implicated in coronary artery endothelial damage. We placed 16 neonatal (age 1 to 3 days) Duroc piglet hearts on an isolated nonworking perfusion circuit. Endothelium-dependent and endothelium-independent vasodilation were tested by measuring coronary blood flow after intracoronary infusion of bradykinin (10(-6) mol/L) and nitroprusside (10(-6) mol/L), respectively. In addition, nitric oxide levels were measured after bradykinin infusion. The hearts were then arrested blindly with either a modified University of Wisconsin solution (group 1; n = 8, K+ = 25 mEq/L) or standard University of Wisconsin solution (group 2; n = 8, K+ = 129 mEq/L) by infusion of cardioplegic solution every 20 minutes for a total of 2 hours. After bradykinin infusion, the mean coronary blood flow increased by 237.1% +/- 14.0% of baseline valves before arrest and by 232.8% +/- 16.0% after arrest in group 1 (p = not significant). As in the first group, the mean coronary blood flow in group 2 increased by 231.1% +/- 13.7% before arrest; however, the increase in mean coronary blood flow after arrest was significantly attenuated (163.3% +/- 12.8%, p < 0.01). The loss of endothelium-dependent coronary blood flow response in group 2 correlated with a decreased capacity to release nitric oxide after arrest (prearrest 8.25 +/- 2.30 nmol/min per gram versus postarrest -2.46 +/- 2.29 nmol/min per gram, p < 0.01). Endothelium-independent vasodilatory response revealed no significant difference between groups before and after arrest. These results suggest that the low-potassium University of Wisconsin solution provides superior protection of the endothelium by preserving the endothelium-dependent vasodilatory response to nitric oxide release.

Adenosine↗
PubMed1997

Continuous antegrade warm blood cardioplegia attenuates augmented coronary endothelium-dependent contraction after cardiac global ischemia and reperfusion.

BACKGROUND: Experiments were designed to evaluate the effect of warm blood cardioplegia on endothelium-dependent contraction of the coronary endothelium after cardiac global ischemia and reperfusion. METHOD: Dogs (n = 12 in each group) were exposed to extracorporeal circulation with the body temperature at 37 degrees C (group 1) or 28 degrees C (groups 2 and 3). The ascending aorta was crossclamped for 120 minutes while continuous infusion of warm blood cardioplegec solution (group 1) or intermittent infusion of cold (4 degrees C) crystalloid cardioplegic solution (group 2) was performed via the coronary arteries through the aortic root. Cardioplegic solution was not used in group 3 animals. The heart was then allowed to function for 60 minutes of reperfusion. Reperfused (groups 1, 2, and 3) and control (group 4) coronary arteries were then harvested for study. RESULTS: Perfusate hypoxia caused endothelium-dependent contraction in the arteries of all four groups that could be attenuated by NG-monomethyl-L-arginine (L-NMMA) or L-NMMA plus D-arginine, but not by L-NMMA plus L-arginine or endothelin receptor A and B antagonist PD 145065. The endothelium-dependent contraction results in groups 2 and 3 (75% +/- 4% and 80% +/- 5%, respectively) were significantly greater than those in groups 1 and 4 (15% +/- 3% and 18% +/- 5%, respectively). Scanning electron microscope studies showed that platelet adhesion and aggregation, areas of microthrombi, disruption of endothelial cells, and separation of the intercellular junction could be found in coronary segments from groups 2 and 3, but not in vessels from groups 1 and 4. CONCLUSION: These experiments suggest that global ischemia and reperfusion enhances hypoxia-mediated endothelium-dependent contraction of the coronary endothelium and damages the ultrastructure. These kinds of changes can be prevented by continuous antegrade infusion of warm blood cardioplegic solution during global ischemia.

Animals↗
PubMed1983

Mapping of the bone marrow sinus endothelium with lectins and glycosylated ferritins: identification of differentiated microdomains and their functional significance.

The distribution of lectin binding sites and sugar-recognizing systems (lectin-like substances) was studied on the luminal side of the bone marrow sinus endothelium in rats. Ferritin-conjugated lectins (Con A, PHA, RCA, WGA, UEA) and glycosylated ferritins (mannosyl, fucosyl, chitobiosyl) were used as probes. With the exception of UEA, all lectins bound to the endothelial surface. The binding was heavier on the plasmalemma proper of the nuclear region (PP-N) compared to that of the tapered region (PP-T). Lectin mapping also identified differentiated microdomains with less or no bindings. These domains related to the transport organelles in the endothelium: luminal vesicles (LV) and diaphragmmed fenestrae (DF). The relative density of binding for these four domains demonstrated the following spectrum PP-N greater than PP-T greater than LV greater than DF. The relation of this binding pattern to the transport function of marrow sinus endothelium for various cells and molecules has been discussed. Lectin mapping also identified heavily labeled microvilli and microprojections from the membrane. These organelles may have a function in recognizing cells and molecules for the transport. The absence of binding for UEA, also absent in liver endothelium, may differentiate sinus endothelia from other endothelia. This lectin is thought to be endothelium-specific in other systems. No binding was observed with glycosylated ferritins suggesting the absence of lectin-like substances on marrow sinus endothelium.

Affinity Labels↗
PubMed1992

Diabetes mellitus impairs neurogenic and endothelium-dependent relaxation of rabbit corpus cavernosum smooth muscle.

The effect of alloxan-induced diabetes on the reactivity of corporeal nerves, endothelium and smooth muscle was studied in the New Zealand white rabbit. Fifteen rabbits were randomly divided into treated (n = 6) and control (n = 9) groups. The treated group was maintained for 6 weeks. Two control groups were studied. One control group (n = 3) was maintained for 6 weeks as littermate controls for diabetic group. The second control group (n = 6) was not maintained but was weight matched with the 6 week diabetic group. The reactivity of corpus cavernosum tissue from the diabetic animals and the control animals was studied in organ chambers. When tissue contraction was produced with phenylephrine for the study of relaxation to various stimuli, the tension induced was similar in the diabetic and the control groups. Relaxation of corpus cavernosum tissue to electrical stimulation of autonomic nerves as well as relaxation to the endothelium-dependent vasodilator acetylcholine were comparably unaffected in the weight matched and littermate control groups while significantly inhibited in the diabetic group. Treatment of the corporeal tissue with the cyclooxgenase inhibitor indomethacin enhanced the relaxation to electrical stimulation and to acetylcholine in the control and in the diabetic groups but did not improve the significant difference in relaxation between the two groups. Relaxation of corporeal tissue to endothelium-independent vasodilators, papaverine and nitroprusside was similar in the control groups and the diabetic groups. It is concluded that diabetes impairs neurogenic and endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. These findings are comparable to those described in corpus cavernosum tissue from diabetic men, showing the validity of this experimental animal model. The mechanism for the nerve or endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the ability of the corporeal smooth muscle to relax via a cGMP-dependent mechanism. Since nitric oxide has been shown to act as the nonadrenergic noncholinergic neurotransmitter as well as endothelium-derived relaxing factor (EDRF) of the trabecular smooth muscle, it is possible that impairment of neurogenic and endothelium-dependent relaxation due to diabetes is mediated by alteration in the synthesis or availability of nitric oxide in corporeal tissue.

Acetylcholine↗
PubMed2002

Effects of catechins on vascular tone in rat thoracic aorta with endothelium.

The effects of eight catechin derivatives on vascular tone in rat thoracic aorta were examined. Catechin derivatives (10 microM) potentiated the contractile response to phenylephrine in endothelium-intact arteries. The potentiations produced by EGCg and EGC were almost absent in endothelium-denuded arteries and abolished by N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis. The catechin derivatives also inhibited endothelium-dependent relaxation in response to acetylcholine. The order of catechin derivatives ranked in terms of both increasing vascular reactivity and impairing endothelium-dependent relaxation was similar; (-)-gallocatechin (GC) >or= (-)-epigallocatechin (EGC) >or= (-)-gallocatechin gallate (GCg) >or= (-)-epigallocatechin gallate (EGCg) >or= (-)-catechin (C) >or= (-)-epicatechin (EC) >or= (-)-catechin gallate (Cg) >or= (-)-epicatechin gallate (ECg). In addition, EGC inhibited the endothelium-independent relaxation evoked by both sodium nitroprusside and NOC-7, a spontanous NO releaser, but EGCg inhibited only that by NOC-7. These findings indicate that catechin derivatives produce a potentiation of the contractile response and an inhibition of the vasorelaxant response, probably through inactivation of endothelium-derived nitric oxide (NO), and that the hydroxyl on C-5 of the B ring together with the stereoscopic structure between the C-3 group and the B ring of flavanols was of importance in mediating the above effects and that the substitution of a gallate group of C-3 attenuated the effects, probably due to a decreased response to solube guanylate cyclase in vascular smooth muscle cells.

Animals↗
PubMed1997

Influence of endothelium in contraction induced by phorbol ester in isolated rat aortic rings.

The present study aimed to investigate the possible role of endothelium in contractile response to phorbol 12,13-diacetate (PDA) by measuring the contractile force in rat isolated aortic rings. PDA at low concentrations induced small and sustained tension in arteries with intact endothelium. N(G)-Nitro-L-arginine (100 microM), a nitric oxide synthase inhibitor and methylene blue (10 microM), an O2-generator induced a large increase in tension in the presence of PDA. The magnitude of contractions in response to N(G)-Nitro-L-arginine was related to concentrations of PDA. Staurosporine (10 nM), an inhibitor of protein kinase C completely inhibited contractile response to PDA as well as potentiating effects of N(G)-Nitro-L-arginine and methylene blue. Removal of the endothelium abolished contractile responses to both N(G)-Nitro-L-arginine and methylene blue in the presence of PDA. Removal of extracellular Ca2+ suppressed contractile responses to both PDA and N(G)-Nitro-L-arginine. On the other hand, N(G)-Nitro-L-arginine (100 microM) did not induce contractions of the rat aorta pre-treated with 4-alpha-phorbol 12-myristate 13-acetate, an inactive form of phorbol ester. Acetylcholine concentration-dependently induced reduction of tension induced by PDA (0.3 microM) in rat aorta. N(G)-Nitro-L-arginine or removal of endothelium prevented the effect of the acetylcholine-induced relaxation. Indomethacin (1 microM), glibenclamide (3 microM) and charybdotoxin (100 nM) did not affect the PDA response in rat aorta. These results indicate that in rat aorta, the basal release of nitric oxide could modulate the PDA-induced contraction, which is likely to accounts for the smaller contractile response induced by PDA in arteries with intact endothelium compared to much larger contractions seen in arteries without endothelium.

Acetylcholine↗