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Biomedical subjects

V A Alder

Publications and source records attributed to V A Alder.

At least 19 recordsLinked to original sources
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↗
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

Localization of IgG in the normal and dystrophic rat retina after laser lesions.

PURPOSE: To test the hypothesis that access to extravasated plasma protein IgG may influence photoreceptor survival following laser photocoagulation and to determine whether this correlates with the retinal glial reaction. METHODS: A total of 45 rats (18 Royal College of Surgeons (RCS) dystrophic and 18 RCS-rdy+ congenic control) were used for this experiment. Nine non-lasered littermates of same age were used as controls. The superior retinas of postnatal day 23 rats were irradiated with a grid pattern of 40 argon green laser lesions of 50 microm in diameter and two powers (150 and 300 mW) for 0.2 s. At various times after laser lesions (up to 14 days), animals were perfused, the retinas snap frozen and sectioned on a cryostat. A one-step immunohistochemical technique was used by incubating with rabbit anti-rat IgG conjugated directly to horseradish peroxidase. Adjacent sections were processed using an antibody to glial fibrillary acidic protein (GFAP) by the standard avidin-biotin complex method. RESULTS: The labelling pattern for extravasated IgG after laser lesion was very similar in both RCS and RCS-rdy+ rat retinas. At 6, 12 and 24 h after lesions, IgG immunoreactivity (IR) was very intense in the lesion core and flanks. The outer plexiform layer (OPL) and photoreceptor inner segments provided a ready pathway for lateral spread of IgG. However, in the outer nuclear layer (ONL), IgG localization was much more restricted. Despite very intense IgG IR in the ONL of the coagulated lesion core, there was always a very sharply delineated boundary where the label abruptly halted. The GFAP labelling in both RCS dystrophic and RCS-rdy+ congenic control rat retinas showed that this boundary was between normal and necrotic cells because there was a core where GFAP was not produced by Müller cells. By 2 days after lesions, the coagulated cells in the lesion core were being removed by phagocytic cells that were IgG IR. Labelled phagocytic cells were also found among the inner and outer segment region on the lesion flanks. There was still IgG IR in the lesion, but the label was faint. No IgG IR was found in the retina at 3, 4, 7 and 14 days after lesions. Absorption control with pure rat IgG showed the label to be specific. CONCLUSIONS: The extravasated IgG was derived from the choroidal circulation because at no stage was IgG localized around the retinal vasculature. The IgG labelling was surprisingly widespread and, therefore, did not correlate with photoreceptor sparing, although it preceded the widespread Müller cell expression of GFAP and may, therefore, trigger glial reaction.

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

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

Culture and characterization of smooth muscle cells from porcine retinal microvessels.

PURPOSE: To establish long-term cultures of retinal vascular smooth muscle cells for future studies of their functions under normal and diseased conditions. METHODS: Smooth muscle cells (SMC) from porcine retinal microvessels were isolated and cultured. RESULTS: Cells in culture retained the common biochemical characteristics of SMC propagated from other sources. The cells were large, polygonal, spindle shaped and demonstrated the presence of smooth muscle-specific alpha-actin. Post-confluent cultures showed the 'hill and valley' multilayer growth characteristics. However, the growth rate was lower and the population doubling time was significantly larger than those reported for SMC propagated from big vessels. CONCLUSION: Retinal vascular SMC could be cultured separately from other cell types. The availability of this culture provides a unique model for functional and metabolic studies of the retinal vessels.

Actin Cytoskeleton↗
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↗
PubMed1998

Relation between pressure determined by ophthalmodynamometry and aortic pressure in the dog.

AIMS: Ophthalmodynamometry has been used extensively since the last century; however, controversy surrounds what it actually measures. This study was set up to determine the relation between ophthalmodynamometric (ODP) and systemic blood pressures. METHODS: Aortic pressure was continuously monitored and altered by phlebotomy in six anaesthetised dogs, while ophthalmodynamometry was performed, by directly altering intraocular pressure. Maxillary artery pressure was monitored in two animals. All pressure transducers were zeroed at eye level. RESULTS: Mean ODP was 96.6% (1.6%) (95% confidence interval, n = 49) of aortic pressure. Mean maxillary artery pressure was 95.7% (5.5%) (95% CI, n = 16) of aortic pressure. ODP was 1.9 (0.6) mm Hg (95% CI, n = 33) higher than maxillary artery pressures. CONCLUSION: ODP was only slightly below aortic pressure and not significantly different from maxillary artery pressure, the analogue of the internal carotid artery in humans. These results also suggest a retinal artery collapse pressure of at least 1.9 mm Hg.

Animals↗
PubMed1998

Intraretinal oxygen distribution in urethan-induced retinopathy in rats.

This study was performed to explore the interaction between chronic neural degeneration and the subsequent vascular remodeling. Weekly urethan administration in rats from birth produces a retinopathy model characterized by photoreceptor degeneration, retinal vascular regression, and retinal pigment epithelium (RPE) neovascularization. We investigated the hypothesis that altered oxygen distribution across the retina and choroid could be involved in the vascular changes seen in this retinopathy. We compared measurements of vitreal, intraretinal, and choroidal oxygen tension (PO2) distribution in anesthetized and ventilated control and urethan-treated rats at 8 and 16 wk of age with the use of oxygen-sensitive microelectrodes. Striking differences were observed in both choroidal and intraretinal PO2 distribution in urethan-treated rats compared with controls. At both ages, intrachoroidal PO2 was much lower in the urethan-treated rats. In addition, the intraretinal PO2 distribution across the inner retinal layers was more uniform than normal. A small elevation in PO2 was present at 8 wk in the inner nuclear layer where subsequent vascular regression occurred, and a small reduction in PO2 was present at the RPE, which recovered to normal values by 16 wk in regions where RPE vessel networks were first evident. Although the retinal arteries were considerably thinner at both ages in the urethan-treated rats, the vitreal PO2 profiles and superficial retinal PO2 remained normal. The unexpected and large reduction in the oxygen delivery from the choroid found in the urethan-treated rats may account for the lack of major hyperoxia within the pathological retina and the lower oxygen tension in the RPE before the vascular proliferation in this region. We propose that tissue PO2 is an important determinant of the vascular remodeling, which is seen in this model of neural degeneration and that the PO2 distribution changes described in this study help provide a new view of the pathogenesis of this model.

Animals↗
PubMed1998

The correlation between cerebrospinal fluid pressure and retrolaminar tissue pressure.

PURPOSE: To measure the effects of cerebrospinal fluid pressure (CSFp) on retrolaminar tissue pressure (RLTp) and the translaminar pressure gradient (TLPG), particularly at low CSFp, which is the normal situation in erect posture. METHODS: Micropipettes coupled to a servonull pressure system were passed into eyes of anesthetized dogs to the optic disc and advanced in steps through the lamina cribrosa to the optic nerve subarachnoid space (ONSAS), while pressure measurements were taken. Cerebrospinal fluid pressure and intraocular pressure (IOP) were monitored and controlled. The TLPG was measured at varying IOPs and CSFps. The RLTp and ONSAS pressure (ONSASp) were measured at varying CSFps. In separate experiments, the optic nerve dura was incised, and pressure measurements were taken across the pia mater. RESULTS: The TLPG was strongly correlated to the difference between IOP and CSFp (r=0.93; n=18) when CSFp was more than zero. Mean RLTp was 3.7+/-0.2 mm Hg (SEM; n=15) when CSFp was 0 mm Hg. The ONSASp and RLTp were largely dependent on the presence of CSFp higher than break point pressures of -0.5 mm Hg and 1.33 mm Hg, respectively. However, below these break points, RLTp (slope 0.07) and ONSASp (slope 0.18) were little influenced by CSFp. Separate measurements across the pia mater revealed that 95% of the pressure drop occurred within 100 microm of the pial surface. CONCLUSIONS: The TLPG and RLTp are dependent on CSFp when CSFp is more than -0.5 mm Hg. Below this level, there is no hydrostatic continuity between the intracranial and optic nerve subarachnoid space. In this range, RLTp is stable and is little influenced by CSFp changes.

Animals↗
PubMed1997

Heterogeneous endothelial cell structure along the porcine retinal microvasculature.

The pivotal role of the endothelial cell in the regulation of vascular tone has been well demonstrated in many vascular beds, including the retina. However, in the retina, little is known about how the structural elements of the endothelial cells are arranged along the arborisation pathway from artery to vein, the nature of which has been linked to functional heterogeneity in other vascular beds. The relative vulnerability of the retina to vascular based diseases, and the heavy reliance on local regulation of the retinal vasculature makes an improved understanding of such local regulatory mechanisms of significant clinical importance. The present study focuses on identifying differences in endothelial cells along the arborisation pathway in the porcine retinal vasculature. Enucleated pig eyes were arterially cannulated and perfused with fixative followed by double staining for F-actin microfilaments (rhodamine phalloidin) and nucleic acid (YO-PRO-1). The intact retina was then viewed by confocal microscopy. The distribution of F-actin, vessel diameter, endothelial cell size and shape, nucleus size and shape, and position within the cell were determined as a function of location along the vascular tree. The main retinal arterioles (A1) contained full length F-actin internal stress fibers which lay parallel to the long axis of the endothelial cell. Subsequent branches from the A1 arteriole (A2 and A3) showed fewer, shorter fibers, with none visible in the A4 and A5 branches, the capillaries, or in the venous side of the vasculature. All endothelial cells showed peripheral border staining of F-actin microfilaments which allowed the shape of the cell to be determined. All endothelial cells were elongated with the long axis parallel to the vessel, but the mean aspect ratio decreased from 10.9+/-0.5, s.e.m. in the A1 arterioles to 3.2+/-0.2 in the major veins (V1). The position of the endothelial cell nucleus relative to the cell was eccentric in the downstream direction in the A2-A5 arterioles, whilst centrally placed in the A1 arterioles and veins. The structural heterogeneity of endothelial cells along the pig retinal circulation suggests that functional heterogeneity of the endothelium may be involved in regulation of retinal blood flow.

Actin Cytoskeleton↗
PubMed1997

Retinal artery and vein pressures in the dog and their relationship to aortic, intraocular, and cerebrospinal fluid pressures.

The relationship between retinal arterial (Pra) and aortic (Pa) pressures is unknown, and the relationship between retinal vein (Prv) pressure and intraocular pressure (IOP) is not clear. Also unclear is the effect of cerebrospinal fluid pressure (CSFp) upon retinal venous pressure. We aimed to measure the relationships among Pra, Prv, Pa, IOP, and CSFp. Dogs were anesthetized while IOP, CSFp, and Pa were monitored. Pipettes with 2.5-micron diameter tips, connected to a servonulling pressure transducer, were used to record pressures from the retinal arteries and veins. Across a range of IOP (16-22 mmHg), CSFp (0-21 mmHg), and Pa (23-195 mmHg) the Pra = 0.72 Pa + 4.3 (r = 0.99, n = 61, P < 0.01), which suggests that the relationship between Pra and Pa is linear over a broad range of systemic blood pressures. The correlation coefficient between Prv and IOP was greater than 0.96 (P < 0.01) at all venous sites and whether IOP was greater than or less than CSFp. The transmural pressure varied along the retinal vein from 1.3 +/- 0.3 mmHg (+/-95% CI, n = 30) at 1 disk diameter from the optic disk rim to 0.3 +/- 0.2 mmHg (n = 66) at the optic disk, with a 0.9-mmHg/mm pressure gradient. These are the first measurements demonstrating a retinal vein transmural pressure close to zero.

Animals↗
PubMed1997

Measurement of vasoactivity in the guinea-pig choroid.

PURPOSE: A perfusion system for studying the vasoactive properties of the guinea-pig choroid is described. METHODS: The principle of operation is that the vascular resistance of the entire vascular network of an isolated, perfused eye can be monitored by recording the pressure required to deliver a constant flow of perfusate through the network. Delivery of the pharmacological agent of interest into the perfusate stream and the subsequent determination of the magnitude of any induced pressure changes allows the vasoactive potency of various agonists to be assessed. RESULTS: The baseline vascular resistance was 1.35 +/- 0.16 mmHg min/microL (mean +/- SEM; n = 10) and the mean response to intraluminal delivery of 124 mmol/L K+ Krebs was an increase in resistance of 297 +/- 67%. Vasoactive responses were sustainable for more than 8 h. CONCLUSIONS: This system will now be used to study the vasoactive properties of the guinea-pig choroid in greater detail.

Animals↗
PubMed1996

Asymmetrical response of the intraluminal and extraluminal surfaces of the porcine retinal artery to exogenous adenosine.

The relative effects of exogenous adenosine applied intraluminally or extraluminally were compared on first-order pig retinal arteries in an isolated perfused artery preparation. First-order retinal arteries with at least one side branch were cannulated and perfused at a constant flow in an environmentally-controlled organ bath on the stage of an inverted microscope. Vessels were precontracted with 10(-4) methoxamine applied extraluminally, which produced a sustained contraction. Then, either extraluminal or intraluminal adenosine was added in increasing concentrations from 10(-9) to 10(-3) M. During these procedures continuous measurements of external vessel diameter were made. The average external diameter of the retinal arterial segments used was 127.6 +/- 2.3 microns (n = 13). Extraluminal methoxamine (10(-4) M) constricted the vessels to 77.9 +/- 2.0% (n = 9) and 78.8 +/- 0.8% (n = 4) of the control value for the vessels later exposed to extraluminal and intraluminal adenosine respectively. Extraluminal adenosine caused a dose-dependent dilatation which commenced between 10(-7) M and 10(-6) M, and reached a percentage dilatation of 22.6 +/- 1.8% (n = 9) at 10(-3) M. For concentrations of 10(-4) M and above, spontaneous oscillations in diameter were observed for extraluminally-applied adenosine with an average period of 0.46 +/- 0.02 (n = 9) cycles per minute. The average percentage diameter oscillation was +/- 7.1% of the mean diameter. In contrast, intraluminal adenosine failed to cause dilatation or spontaneous oscillations at all concentration values, although the dilatory ability of these vessels was confirmed by intraluminal application of the Ca2+ channel blocker verapamil. In conclusion this study has demonstrated that the two sides of the retinal artery wall are differentially sensitive to adenosine, with the intraluminal route being ineffective. In vivo, in hypoxic or ischemic situations, adenosine is released by extraluminal neural tissue and minimizes tissue damage, partially by acting as a signaller of metabolic status to the vasculature leading to vasodilatation and hence increased local blood flow. This study shows that delivery of adenosine for therapeutic purposes through an intraluminal route is not a feasible proposition. This isolated, perfused artery technique has considerable potential to improve our understanding of uptake mechanisms, metabolism and vasoactivity of the retinal vessel wall.

Adenosine↗
PubMed1996

Intraretinal oxygen distribution and choroidal regulation in the avascular retina of guinea pigs.

O2-sensitive microelectrodes were used to measure PO2 as a function of depth through the retina and choroid of anesthetized and artificially ventilated guinea pigs. The guinea pig retina is of particular interest, because it has a typically mammalian structure but no retinal circulation; it relies totally on choroidal delivery of O2 and other nutrients. Measurements of intraretinal O2 distribution in an avascular mammalian retina have not previously been reported. Under normal ventilation conditions, PO2 decreased monotonically from the choroid (33.6 +/- 2.9 mmHg, n = 11) to near zero (0.4 +/- 0.1 mmHg) at the retina-vitreous boundary. The inner half of the retina had an average PO2 of only 0.6 +/- 0.1 mmHg. Stepwise increases in inspired O2 (from 20 to 40 to 60 to 80 to 100%) had surprisingly little effect on choroidal PO2. Rapid changes (20-100%) produced overshoot-type responses in the choroid before recovery to levels only slightly above those found in normoxia. This indicates the presence of an active O2-regulatory mechanism in the guinea pig choroid. Addition of CO2 (5%) to O2 ventilation appeared to break down this control mechanism and led to dramatic and sustained increases in PO2 throughout the retina and choroid. The demonstration of an O2-regulating mechanism in the guinea pig choroid that maintains choroidal PO2 well below that in the systemic arterial blood, coupled with the observation of very low O2 levels throughout the inner retina, suggests that the O2 requirement of the inner retina in the guinea pig is small and that O2 levels in the choroid are deliberately constrained.

Animals↗
PubMed1996

Direct vasodilatory effect of insulin on isolated retinal arterioles.

PURPOSE: To test the hypothesis that insulin has a direct vasodilatory effect on retinal arteries and their branches and to investigate the mechanisms involved. METHODS: Segments of porcine retinal arteries were dissected, cannulated, and perfused. Vessel diameter was measured continuously on-line. Vessels were precontracted to 66% +/- 0.9% (SEM, n = 148) of their original diameter by perfusing with 124 mM K(+)-Krebs solution. Dose-response curves to insulin (2 to 2000 microU/ml) were compared for extraluminal (EL), intraluminal (IL), and combined IL-EL application. The effect of cyclooxygenase and nitric oxide synthase inhibition on the insulin response was determined, as was Ca2+ channel involvement. RESULTS: EL insulin alone had no significant effect on vessel diameter. IL insulin produced a dose-dependent dilatation of 5.6% +/- 2.9% (n = 22) of the K+ contracted diameter at 200 microU/ml and up to 12.4% +/- 3.6% (n = 22) by 2000 microU/ml, whereas combined IL-EL insulin application caused dilatation at all concentrations, rising to 15.1% +/- 2.9% (n = 44) at 200 microU/ml and 19.7% +/- 3% (n = 44) at 2000 microU/ml. IL indomethacin (5 x 10(-5) M) had no significant effect on the insulin-induced dilatation, whereas IL L-NAME (10(-4) M) inhibited insulin dilatation completely. The addition of EL verapamil (10(-6) M) during insulin-induced dilatation resulted in further dilatation to 37.8% +/- 4.2% (n = 18). However, the addition of insulin to verapamil-dilated vessels caused no further dilatation. Exposure to EL insulin while the IL K+ contraction dose-response curve was measured had no effect. Results in main arteries and branches did not differ. CONCLUSIONS: The IL application of insulin dilates potassium-contracted pig retinal arteries. This effect was enhanced by the EL presence of insulin, which did not result in dilatation when it was administered alone. The dilatation response was mediated by nitric oxide but not by prostaglandins. There was some evidence for the involvement of Ca2+ channels in insulin-induced dilatation. These results imply that insulin is a vascular regulator in normal conditions and may have relevance to the vascular changes occurring in diabetes and hypertension in the retina.

Animals↗