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E N Su

Publications and source records attributed to E N Su.

At least 19 recordsLinked to original sources
PubMed2002

Agonist-induced vasoactive responses in isolated perfused porcine dental pulpal arterioles.

A novel isolated perfused pulpal arteriole preparation and microperfusion system was used to evaluate the direct vasoactive responses of pulpal arterioles to selected agonists. Short lengths of porcine pulpal arterioles (101.7+/-2.2 microm o.d., n=105) were dissected out and placed in an environment-controlled bath on the stage of an inverted microscope. Both ends of the vessel were cannulated and perfused at a controlled rate through the lumen. The diameter of the vessel was measured online. Following equilibration, the vessel was challenged with various agonists: adrenaline (epinephrine), noradrenaline (norepinephrine), phenylephrine, dopamine, isoproterenol, 5-hydroxytryptamine, histamine and adenosine. The endothelium-dependent vasodilator acetylcholine was used to evaluate endothelial cell function. Adrenaline, noradrenaline, phenylephrine, 5-hydroxytryptamine and dopamine caused dose-dependent contractions (adrenaline=noradrenaline>phenylephrine>dopamine>5-hydroxytryptamine). Isoproterenol and histamine provoked a dose-dependent dilation. Adenosine produced pronounced vasodilatation in vessels precontracted with 10(-8)M endothelin-1. Functional adrenergic, histamine, 5-hydroxytryptamine and adenosine receptors are, therefore, present in porcine pulpal arterioles. The isolated perfused pulpal arteriole preparation may prove valuable in understanding local control mechanisms of pulpal microcirculation.

Adenosine↗
PubMed2002

An in vivo and in vitro comparison of the effects of vasoactive mediators on pulpal blood vessels in rat incisors.

The effects of endogenous vasoactive substances were evaluated in anaesthetized rats using a laser Doppler flowmeter to monitor changes in pulpal blood flow, as well as directly in isolated pulpal arteriole preparations utilising a microperfusion and monitoring system to observe changes in vessel diameter. In anaesthetized rats, while systemic arterial blood pressure remained relatively stable, intra-arterial delivery of adrenaline (epinephrine) (A), noradrenaline (norepinephrine) (NA), phenylephrine (PHE), dopamine (DOPA), 5-hydroxytryptamine (5-HT), or endothelin-1 (ET-1) produced a dose-dependent reduction in pulpal blood flow (order of potency: ET-1>>A=NA>PHE=DOPA=5-HT); acetylcholine induced a dose-dependent increase in pulpal blood flow; histamine, isoproterenol and adenosine produced no significant changes. In isolated arteriole preparations, intraluminal delivery of A, NA, PHE, DOPA or 5-HT produced dose-dependent vasoconstriction (A=NA>PHE=DOPA=5-HT). Acetylcholine relaxed NA-precontracted vessels dose-dependently. Histamine and isoproterenol produced a small vasodilatation. Intraluminal ET-1 produced a small vasoconstriction at 10(-8)M, whereas extraluminal ET-1 produced a dose-dependent vasoconstriction from 10(-10)M and above. Intraluminal adenosine failed to dilate vessels precontracted with ET-1, whereas extraluminal adenosine caused a complete relaxation. These combined in vivo and in vitro data suggest that, in the rat incisor, the pulpal microcirculation is capable of functional regulation and that pulpal blood flow may be modulated by endothelium-related factors, metabolic (tissue-related) factors, as well as humoral (blood-borne) factors.

Analysis of Variance↗
PubMed2001

Pathogenesis and intervention strategies in diabetic retinopathy.

Diabetic retinopathy is the leading cause of new blindness in the working-age population. If improved treatment regimens are to be developed it is crucial that the underlying pathophysiological mechanisms responsible for diabetic retinopathy are better understood. The multifactorial nature of the many pathways implicated in diabetic retinopathy requires a very detailed approach to elucidate the key mechanisms involved and their interactions in order to develop logical strategies aimed at therapeutic intervention. Fortunately, the streptozotocin rat model of diabetes displays many of the morphological and functional changes to the retinal vasculature that are evident in human diabetic retinopathy. This study reviews some of the recent experimental work by the authors in the streptozotocin rat, compares their findings to the human pathology and outlines potential new avenues for therapeutic intervention. In particular the improved understanding of which layers of the inner retina have the most stringent metabolic demands has helped identify which retinal layers are most susceptible to metabolic or hypoxic/ischaemic insult. It is concluded that improved treatment outcomes may ensue if the therapy is targeted at the appropriate tissue at specific stages of the disease.

Animals↗
PubMed2001

Tetrahydrobiopterin reverses the impairment of acetylcholine-induced vasodilatation in diabetic ocular microvasculature.

The purpose of this study is to test whether tetrahydrobiopterin, an essential cofactor in nitric oxide synthesis, can reverse endothelium dysfunction in diabetic ocular circulation. Using the streptozotocin-induced diabetic rat model and the isolated perfusion eye technique, the response to the acetylcholine (an endothelium-dependent vasodilator mediated by stimulated nitric oxide release) induced vasodilatation of the diabetic ocular vasculature before and after tetrahydrobiopterin administration was compared. Age matched normal rats were used for reference response. Six streptozotocin-induced diabetic rats and eleven control rats at 21.5 +/- 0.2 weeks and 21.2 +/- 2.1 weeks postinduction, respectively, were used. The dose response curve from the diabetic eyes was found to be significantly different from that of the control eyes (p < 0.001) with significantly reduced responses to 10(-4)M acetylcholine. After 30 min of administration of tetrahydrobiopterin to the diabetic eyes, however, the acetylcholine-induced vasodilatation response was significantly (p < 0.001) increased compared with the response prior to tetrahydrobiopterin administration. The vasodilatory response in the diabetic eyes after tetrahydrobiopterin administration was at a level that was comparable with the control response (p = 0.742). We have shown that acute administration of tetrahydrobiopterin is effective in reversing to control level the impaired acetylcholine-induced vasodilatory response at 21.5 +/- 0.2 weeks postinduction. Our result suggests that a decreased level of tetrahydrobiopterin in the eyes of the streptozotocin-induced diabetic rats may be responsible for the ocular vascular endothelium dysfunction.

Acetylcholine↗
PubMed2001

Acetylcholine-induced vasodilation of isolated pulpal arterioles.

The presence of cholinergic mechanisms in the control of pulpal microcirculation has been a controversial issue. In this study, we aimed to determine the direct vasoactive responses of isolated pulpal arterioles to acetylcholine, and to investigate whether such responses are endothelium-dependent. Using an in vitro micro-perfusion system, we isolated pig pulpal arterioles, cannulated and perfused them intraluminally, and monitored the diameter. Following equilibration, the vessels were contracted with 10(-5) M noradrenaline, and the effect of increasing doses of acetylcholine was determined. The influence of the muscarinic antagonist, atropine, or the loss of endothelial cell function following saponin treatment was also determined. Acetylcholine induced a dose-dependent vasodilation, reaching 94.6+/-1.4% (n = 22) of the uncontracted diameter at 10(-4) M. The vascular relaxation effect of acetylcholine was abolished in the presence of atropine, and by saponin treatment. Analysis of these data suggests that, in the pig, the acetylcholine-induced vasodilation of incisor pulpal arterioles is endothelium-dependent and mediated by muscarinic receptors.

Acetylcholine↗
PubMed2001

Comparison of the vasoactive effects of the docosanoid unoprostone and selected prostanoids on isolated perfused retinal arterioles.

PURPOSE: To compare the vasoactive properties of the docosanoid unoprostone, its free acid, and different members of the prostanoid family on isolated perfused pig retinal arterioles to assess their potential to modulate retinal blood flow. METHODS: Segments of porcine retinal arterioles were dissected, cannulated, and perfused, and their diameter monitored during either intraluminal or extraluminal application of increasing doses (10(-10)-10(-4) M) of either the docosanoid unoprostone isopropyl and its free acid or of selected prostanoids: prostaglandin (PG) F(2alpha) and thromboxane A(2) analogue (U46619). Studies were performed on arterioles in their uncontracted state, and also during precontraction with endothelin-1 (10(-9) M). The significance of any induced change in vessel diameter was assessed in relation to the initial vessel diameter or, in the case of endothelin-1 administration, to the contracted diameter with endothelin-1 alone. RESULTS: In normal-tone arterioles without endothelin-1 contraction, PGF(2alpha) and U46619 both produced a potent dose-dependent contraction, but neither unoprostone isopropyl nor unoprostone free acid had a significant vasoactive effect. In endothelin-1-contracted arterioles, U46619 produced further contraction, PGF(2alpha) produced a slight vasodilatation, and unoprostone isopropyl and its free acid produced a pronounced dilatation. CONCLUSIONS: Of the agents tested, unoprostone isopropyl and its free acid were the most potent vasodilators of endothelin-1-contracted pig retinal arterioles. Members of the prostanoid family demonstrated a different effect on the diameter of isolated retinal arterioles compared with the docosanoids. The potential therefore exists for the docosanoid unoprostone to have a beneficial effect on retinal blood flow in addition to any reduction in intraocular pressure.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2000

Continued progression of retinopathy despite spontaneous recovery to normoglycemia in a long-term study of streptozotocin-induced diabetes in rats.

BACKGROUND: This long-term (2.3 years) study determines the temporal relationship between systemic glucose levels and the progression of diabetic retinopathy during the natural course of streptozotocin-induced diabetes in rats. METHODS: Of 367 rats, 200 were randomly assigned into a group injected with streptozotocin (50 mg.kg(-1)) and 167 into a control group. Subsets of the rats were killed at 6, 28, 40, 65, 90 and >100 weeks post induction to allow the severity of retinopathy to be assessed quantitatively and qualitatively by trypsin digests of the retinal vasculature. Concurrently blood glucose, body weight and death rate were monitored. RESULTS: Three glycemic phases were observed in the streptozotocin rats. In phase 1 (0 to 36-40 weeks) hyperglycemia was established and maintained. In phase 2 (36-40 to 84-90 weeks) normoglycemia was restored, and maintained during phase 3 (84-90 to 120 weeks). Control rats were normoglycemic throughout. The retinal microangiopathy was marked at 28 weeks during phase 1, developed more slowly in phase 2 and continued to worsen with loss of capillaries in all retinas and saccular microaneurysms present in 50% of retinas in phase 3. Cumulative death rate in streptozotocin rats also followed three phases, with maximum vulnerability occurring between 28 and 40 weeks. Body weight was significantly lower in streptozotocin rats throughout, increasing slowly in phase 1, then more rapidly during and after spontaneous glycemic recovery. CONCLUSION: The worsening retinopathy, despite sustained recovery to normoglycemia, implies that good glucose control alone does not stop the progression of the retinal microangiopathy at this late stage.

Animals↗
PubMed2000

Acetylcholine-induced relaxation in rat ocular vasculature.

Endothelial cell function is often evaluated by the assessment ofendothelium-dependent relaxation to acetylcholine. The purpose of this study was to characterize the acetylcholine-induced vasodilator responses in the intact ocular vasculature tree in isolated perfused rat eyes. At a fixed perfusion flow rate (5 microl/min), the resultant perfusion pressure reflected the total vascular resistance of the perfused vasculature. The baseline vascular resistance, and hence perfusion pressure, was manipulated by perfusion with high concentrations of potassium Krebs (60, 90, or 124 mM). The response to bolus administration of acetylcholine (10(-8) to 10(-4) M) was then assessed over a range of perfusion pressures. Acetylcholine induced a dose-dependent relaxation response which was larger in magnitude with increased levels of induced vascular tone. The relationship between the size of the acetylcholine-induced response and the baseline perfusion pressure was essentially linear with a correlation coefficient of 0.86 at 10(-5) M and of 0.88 at 10(-4) M acetylcholine. Our results suggest that, in the isolated perfused rat eye, the initial vascular tone has to be considered when evaluating endothelial cell function by acetylcholine-induced relaxation.

Acetylcholine↗
PubMed2000

Intraretinal oxygen levels before and after photoreceptor loss in the RCS rat.

PURPOSE: To measure the intraretinal oxygen environment at different stages in the Royal College of Surgeons (RCS) rat model of retinal degeneration to determine whether changes in oxygen level are an important aspect of the disease. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of depth through the retina of anesthetized, mechanically ventilated RCS rats at ages ranging from postnatal day (P)20 to P104. The oxygen profiles were correlated with histologic observations of the cellular changes within the dystrophic retinas and compared with those in RCS-rdy(+) control animals and published values in normal mature rats. RESULTS: Although the youngest rats studied exhibited some differences in intraretinal oxygen distribution compared with mature animals, the distribution in dystrophic RCS rats at P20 was not significantly different from that in age-matched control subjects. However, the intraretinal oxygen distribution in dystrophic RCS rats was clearly affected after approximately P30, reflecting a loss of photoreceptor oxygen consumption consistent with histologic observations. In contrast, oxygen uptake by the inner retina was still evident long after the loss of photoreceptors was essentially complete. CONCLUSIONS: There was no significant tissue hypoxia during photoreceptor degeneration in the dystrophic RCS rat. The changes in intraretinal oxygen distribution are consistent with the loss of outer retinal oxygen uptake but the preservation of inner retinal oxygen metabolism.

Animals↗
PubMed1999

Systemic and ocular vascular roles of the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers.

This review addresses whether the antiglaucoma agents beta-adrenergic antagonists and Ca2+ entry blockers cause vasoactive effects in the retinal and other ocular vasculatures, as they do in other tissues. The potent vasodilating effects of Ca2+ entry blockers on ocular vessels have recently been demonstrated in in vivo and in vitro studies, implying that the maintenance of ocular vascular tone relies almost exclusively on extracellular Ca2+. Ca2+ entry blockers may potentially play a role in relaxing the retinal, long posterior ciliary, and ophthalmociliary arteries to improve the ocular circulation in vascular diseases in which there is considerable vascular tone present. The beta-adrenergic antagonists are discussed with reference to their antihypertensive role, their effect on other vascular beds, and finally what is known of their effect in the ocular vasculature. The emerging evidence that particular selective beta-adrenergic antagonists, such as betaxolol, are also potent Ca2+ channel entry blockers in other vascular beds is presented. Betaxolol has been shown to induce vasodilatation in the retinal and other ocular vascular beds, although studies have shown that beta1-adrenergic receptors are sparse in these vascular beds. This implies that an alternative mechanism must be responsible for betaxolol-induced vasodilatation. Evidence is presented that betaxolol vasodilates via its potent Ca2+ channel entry blocking properties, and its potency and ability to vasodilate are compared with those of nimodipine and timolol, as well as with those of other Ca2+ channel entry blockers. Important areas for future research in this area are discussed.

Adrenergic beta-Antagonists↗
PubMed1999

Intraretinal oxygen distribution in the rat with graded systemic hyperoxia and hypercapnia.

PURPOSE: To describe the nature of oxygen level changes in specific layers in the rat retina under graded levels of systemic hyperoxia, with and without hypercapnia. METHODS: Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of depth through the retina of anesthetized, mechanically ventilated rats. Breathing mixtures were manipulated to produce stepwise increments in systemic oxygen levels, with or without 5% CO2. Retinal arteriovenous oxygen differences were also measured as an indicator of oxygen delivery through the retinal circulation. Systemic blood gas levels were measured under each condition. RESULTS: Hyperoxia increases PO2 throughout the retina to a varying extent in different retinal layers, with the increase more pronounced in the outer retina than in the inner retina. Simultaneous hypercapnia results in further increases in retinal oxygen levels. The lowest intraretinal oxygen level was consistently found in the inner plexiform layer (IPL), between the two capillary layers that support this region. There was a greater than fourfold increase in oxygen supply from the choroid with hyperoxia but, remarkably, the retinal circulation continued to provide a net delivery of oxygen to the retina. CONCLUSIONS: Hyperoxia results in a significant but nonuniform increase in oxygen level in all layers of the rat retina, which is augmented by hypercapnia. The persistence of a minimum oxygen level in the IPL, despite the dramatic increase in oxygen flux from the choroid, suggests that oxygen consumption increases significantly in the IPL under hyperoxic conditions.

Animals↗
PubMed1999

Light and choroidal PO2 modulation of intraretinal oxygen levels in an avascular retina.

PURPOSE: To determine the influence that choroidal oxygen level and outer retinal oxygen demand have on oxygen availability to the inner retina when the choroid is the only source of retinal oxygenation. This condition prevails in avascular retinas and in vascularized retinas suffering vascular occlusion. METHODS: Oxygen-sensitive microelectrodes were used to measure the oxygen tension as a function of depth in the naturally avascular retina of anesthetized and mechanically ventilated guinea pigs (n = 6). Choroidal PO2 was manipulated by varying the ventilation gas mixture, and outer retinal oxygen consumption was modulated by light-dark adaptation. Individual PO2 profiles were fitted to a multilayer mathematical model of PO2 distribution, and pairs of profiles at different choroidal PO2 levels, or under light and dark conditions, were fitted to an intraretinal PO2 difference model. Both models reflect the purely choroidal supply of retinal oxygenation. RESULTS: An increase in choroidal PO2 produced an equivalent increase in all retinal layers. Light induced a decreased oxygen consumption in the region of the inner segments of the photoreceptors, which resulted in a significant increase in PO2 in this layer, flowing on unattenuated to all inner retinal layers. The intraretinal PO2 distribution and the light- and ventilatory-induced changes in PO2 were consistent with theoretical predictions of the mathematical models. CONCLUSIONS: The present experimental studies confirm that when the choroid is the only source of retinal oxygenation, the full effect of increased choroidal oxygen level or reduced uptake in the outer retina passes through to the inner retinal layers if the oxygen utilization by the inner retina remains constant.

Animals↗
PubMed1998

Effect of betaxolol, timolol and nimodipine on human and pig retinal arterioles.

This study tested the hypothesis that the beta-adrenergic antagonists betaxolol and timolol, cause retinal arteriolar vasodilatation in addition to their ability to reduce intraocular pressure (IOP), and compared their vasodilatory ability with that of a known Ca2+ channel entry blocker nimodipine in donor human and pig isolated perfused retinal arterioles. This study was performed using a microperfusion technique specifically established to allow investigations in arterioles as small as the first order human and pig retinal arterioles (approximately 100 microns diameter). The scarcity of viable human tissue was overcome by the successful development of controlled rate freezing and cryopreservation techniques which were able to preserve the vascular responsiveness of the retinal arterioles, thus enabling multiple experiments to be performed on segments of retinal arterioles from each individual donor eye. Furthermore, relaxation by acetylcholine in noradrenaline contracted pig retinal arterioles showed that endothelial cell function was well maintained after cryopreservation (n = 8). Baseline diameters of retinal arterioles used in the main studies were: cryopreserved human 92.3 +/- 3.4 microns (n = 44), fresh pig 94.7 +/- 2.2 microns (n = 42), and cryopreserved pig 94.3 +/- 2.3 microns (n = 30). Precontraction with extraluminal endothelin-1 (ET-1) 10(-9) M reduced the diameters to 74.3 +/- 0.9%, 71.6 +/- 1.6% and 72.5 +/- 0.9% respectively. Intraluminally applied nimodipine and betaxolol caused a significant dose dependent dilatation (P < 0.001) in human retinal arterioles with a threshold of 10(-12) M. Timolol did not produce a significant dilatation in human arterioles. Timolol produced a small but significant dilatation in fresh and cryopreserved pig arterioles but the dilatation with betaxolol and nimodipine was significantly larger. The nimodipine and betaxolol dose response curves were not significantly different in human arterioles, but nimodipine produced significantly greater dilatation than betaxolol (P < 0.001) in fresh and cryopreserved pig arterioles. Both nimodipine and betaxolol were significantly more effective vasodilators than timolol (P < 0.001) in human and pig retinal arterioles.

Adrenergic beta-Antagonists↗
PubMed1998

Intracellular structures of retinal vascular endothelium in normal and early diabetic rats.

PURPOSE: To determine whether the arrangement of microfilaments in retinal vascular endothelium is altered in early diabetes. METHODS: F-actin and nuclei of retinal vascular endothelial cells of normal and diabetic (28 weeks postinduction) rats were examined using confocal microscopy. RESULTS: An increase in the incidence of aberrant F-actin bundle arrangement in the diabetic retinal arteriole was observed, but there was no disruption of peripheral border F-actin. The diameter of superficial capillaries was increased in diabetic rats. CONCLUSION: These changes may be related to the endothelial dysfunction demonstrated in a previous pharmacological study.

Actins↗
PubMed1998

Preservation of vasoactive properties of human retinal arteries after cryopreservation.

PURPOSE: Although we have several established in vitro systems for studying the vasoactive properties of the ocular vasculature, the restricted availability of human donor tissue has forced us to rely predominantly on animal studies. METHODS: The present paper describes, for the first time, a controlled-rate cryopreservation technique capable of maintaining vasoactive function in human retinal arteries after extended storage. RESULTS/CONCLUSION: The response to constrictive (endothelin-I) and vasodilatory agents (nimodipine and betaxolol) was comparable with that in fresh pig vessels. It is now possible to obtain multiple segments of retinal artery from a single donor eye and to preserve them for detailed pharmacological assessment.

Aged↗
PubMed1998

Quantification of retinal oxygen consumption changes from preretinal oxygen transients.

BACKGROUND: In the avascular retina of the guinea-pig all the oxygen supply is from the choroid. Under these circumstances we had proposed, on theoretical grounds, that a change in retinal oxygen consumption would modulate the preretinal oxygen level. METHODS: In the present study in guinea-pigs,the oxygen consumption of the outer retina was modulated by light-dark exposure while preretinal oxygen tension was monitored. RESULTS: The results were in complete agreement with the proposed mathematical models. CONCLUSION: The present study demonstrates that it is feasible to quantify oxygen consumption changes in a known retinal layer from measurements of preretinal oxygen tension.

Animals↗
PubMed1998

Overview of studies on metabolic and vascular regulatory changes in early diabetic retinopathy.

The present review provides an overview of recent research describing functional changes to the retinal vasculature in very early diabetes. The research focuses on the streptozotocin rat model after 4-6 weeks of induced diabetes and describes functional changes to retinal blood flow, vascular control and retinal oxygenation, as well as a strong vasodilatory response to insulin in the retinal vasculature. The review raises the question of whether choroid dysfunction is also a feature of diabetic retinopathy.

Animals↗