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J W Wright

Publications and source records attributed to J W Wright.

At least 37 records · Page 2Linked to original sources
PubMed1999

Structure-binding studies of the adrenal AT4 receptor: analysis of position two- and three-modified angiotensin IV analogs.

Amino acid substitutions in positions two and three of angiotensin IV (VYIHPF) were carried out to determine which structural features of the side-chains were important for achieving high-affinity binding to bovine adrenal receptors. These studies demonstrated that an activated aromatic ring in the second position side-chain resulted in the highest-affinity binding. Position three required a hydrophobic amino acid to achieve high-affinity binding. Both aliphatic and aromatic side-chains were sufficient to yield high-affinity binding.

Adrenal Glands↗
PubMed1999

The quantitation of lipoprotein lipase mRNA in biopsies of human adipose tissue, using the polymerase chain reaction, and the effect of increased consumption of n-3 polyunsaturated fatty acids.

OBJECTIVE: To examine the effects of the consumption of fish oils on the gene expression of lipoprotein lipase (LPL, EC 3.1.1.34) in human adipose tissue. In order to measure LPL mRNA in adipose tissue samples obtained by needle biopsy from human volunteers a competitive, reverse transcriptase PCR (RT-PCR) protocol was developed. DESIGN: A randomised controlled, single blind cross over dietary study which compared the effects of a low level n-3 polyunsaturated fatty acids (PUFA) using normal foods enriched with eicosapentaenoic (EPA) and docosahexaenoic (DHA) (test diet), with non-enriched but otherwise identical foods (control). The diets were consumed for a period of 22 d with a wash out period of 5 months between the diets. SETTING: Free-living individuals associated with the University of Surrey. SUBJECTS: Six male subjects with a mean (+/- sd) age of 51.2+/-3.6 y were recruited. MAJOR OUTCOME MEASURES: Pre- and postprandial blood samples were taken for the measurement of triacylglycerol (TAG), postheparin LPL activity and adipose tissue samples for the measurement of LPL mRNA levels. RESULTS: Mean LPL expression values were 4.12 x 10(5) molecules of LPL mRNA per ng total RNA on the control diet and 4.60 x 10(5) molecules of LPL mRNA per ng total RNA on the n-3 PUFA enriched (test) diet. There was no significant difference between the levels of LPL expression following each diet, consistent with the lack of change in TAG levels in response to increased dietary n-3 PUFA intake. However, the change in LPL expression (Test-Control diet) correlated significantly with the change in fasting TAG levels (P = 0.03, R = -0.87 and R2 = 0.75) and with the total area under the TAG-time response curve (P = 0.003, R = -0.96 and R2 = 0.92) in individuals. CONCLUSIONS: These findings, although based on a small number of subjects, suggest that LPL expression may be a determinant of plasma TAG levels. The development of this methodology should allow further elucidation of the effects of dietary manipulation and disease processes on lipid clearance and regulation in human subjects.

Adipose Tissue↗
PubMed1999

A role for fasciclin II in the guidance of neuronal migration.

The insect cell adhesion receptor fasciclin II is expressed by specific subsets of neural and non-neural cells during embryogenesis and has been shown to control growth cone motility and axonal fasciculation. Here we demonstrate a role for fasciclin II in the guidance of migratory neurons. In the developing enteric nervous system of the moth Manduca sexta, an identified set of neurons (the EP cells) undergoes a stereotyped sequence of migration along the visceral muscle bands of the midgut prior to their differentiation. Probes specific for Manduca fasciclin II show that while the EP cells express fasciclin II throughout embryogenesis, their muscle band pathways express fasciclin II only during the migratory period. Manipulations of fasciclin II in embryonic culture using blocking antibodies, recombinant fasciclin II fragments, and enzymatic removal of glycosyl phosphatidylinositol-linked fasciclin II produced concentration-dependent reductions in the extent of EP cell migration. These results support a novel role for fasciclin II, indicating that this homophilic adhesion molecule is required for the promotion or guidance of neuronal migration.

Amino Acid Sequence↗
PubMed1999

Structural analysis of angiotensin IV receptor (AT4) from selected bovine tissues.

The angiotensin IV receptor (AT4) receptor is widely distributed in both species and tissues. This broad distribution appears to be reflected in an equally diverse repertoire of physiological actions that are mediated through AT4 receptors. This breadth of location and function of AT4 receptors encourages speculation that multiple AT4 isoforms might exist. In this study, we compared the structural properties of bovine AT4 receptors from adrenals, kidney, heart, thymus, bladder, aorta, and hippocampus. These comparisons were made using polyacrylamide gel electrophoresis or HPLC analysis of AT4 receptors that had been covalently radiolabeled with the AT4-specific photoprobe 125I-benzoyl phenylalamine-angiotensin IV. Except for the hippocampal AT4 receptor, the binding subunit in all tissues had a molecular mass of approximately 165 kDa and associated with additional subunits via disulfide linkages. The hippocampal receptor was significantly smaller (150 kDa) and did not appear to possess other disulfide-linked subunits. The receptor was highly glycosylated in all tissues examined. Peptide mapping following cleavage of 125I-labeled receptor with endopeptidase C or cyanogen bromide resulted in complex cleavage patterns. Together these mapping studies demonstrated the uniqueness of the hippocampal receptor and further suggested that other AT4 isoforms may exist and be variably distributed among bovine tissues. In agreement with the peptide mapping studies, differences in the binding pattern of several AngIV analogs were observed among the various tissues.

Angiotensin II↗
PubMed1999

Markers of intestinally-derived lipoproteins: application to studies of altered diet and meal fatty acid compositions.

BACKGROUND AND AIM: The atherogenic potential of dietary derived lipids, chylomicrons (CM) and their remnants (CMr) is now becoming more widely recognised. To investigate factors effecting levels of CM and CMr and their importance in coronary heart disease risk it is essential to use a specific method of quantification. Two studies were carried out to investigate: (i) effects of increased daily intake of long chain n-3 polyunsaturated fatty acid (LC n-3 PUFA), and (ii) effects of increasing meal monounsaturated fatty acid (MUFA) content on the postprandial response of intestinally-derived lipoproteins. The contribution of the intestinally-derived lipoproteins to total lipaemia was assessed by triacylglycerol-rich lipoprotein (TRL) apolipoprotein B-48 (apo B-48) and retinyl ester (RE) concentrations. METHODS AND RESULTS: In a randomised controlled crossover trial (placebo vs LC n-3 PUFA) a mean daily intake of 1.4 g/day of LC n-3 PUFA failed to reduce fasting and postprandial triacylglycerol (TAG) response in 9 healthy male volunteers. Although the pattern and nature of the apo B-48 response was consistent with the TAG response following the two diets, the postprandial RE response differed on the LC n-3 PUFA diet with a lower early RE response and a delayed and more marked increase in RE in the late postprandial period compared with the control diet, but the differences did not reach levels of statistical significance. In the meal study there was no effect of MUFA/SFA content on the total lipaemic response to the meals nor on the contribution of intestinally derived lipoproteins evaluated as TAG, apo B-48 and RE responses in the TRL fraction. In both studies, the RE and apo B-48 measurements provided broadly similar information with respect to lack of effects of dietary or meal fatty acid composition and the presence of single or multiple peak responses. However the apo B-48 and RE measurements differed with respect to the timing of their peak response times, with a delayed RE peak, relalive to apo B-48, of approximately 2-3 hours for the LC n-3 PUFA diet (p = 0.002) study and 1-1.5 hours for the meal MUFA/SFA study. CONCLUSIONS: It was concluded that there are limitations of using RE as a specific CM marker, apo B-48 quantitation was found to be a more appropriate method for CM and CMr quantitation. However it was still considered of value to measure RE as it provided additional information regarding the incorporation of other constituents into the CM particle.

Adolescent↗
PubMed1998

A delayed role for nitric oxide-sensitive guanylate cyclases in a migratory population of embryonic neurons.

Neuronal differentiation requires a coordinated intracellular response to diverse extracellular stimuli, but the role of specific signaling mechanisms in regulating this process is still poorly understood. Soluble guanylate cyclases (sGCs), which can be stimulated by diffusible free radical gasses such as nitric oxide (NO) and carbon monoxide (CO) to produce the intracellular messenger cGMP, have recently been found to be expressed within a variety of embryonic neurons and implicated in the control of both neuronal motility and differentiation. Using the enteric nervous system (ENS) of the moth, Manduca sexta, we examined the role of NO and NO-sensitive sGCs during the migration and differentiation of an identified set of migratory neurons (the EP cells). Shortly after the onset of their migration, a subset of EP cells began to express NO-sensitive sGC activity (visualized with an anti-cGMP antiserum). Unlike many neurons in the central nervous system, the expression of sGC activity in the EP cells was not transient but persisted throughout subsequent periods of axon elongation and terminal branch formation on the gut musculature. In contrast, nitric oxide synthase activity (visualized using NADPH-diaphorase histochemistry) was undetectable in the vicinity of the EP cells until the period of synapse formation. Manipulations designed to alter sGC and NOS activity in an in vivo embryonic culture preparation had no discernible effect on either the migration or axonal outgrowth of the EP cells. In contrast, inhibition of both of these enzymes resulted in a significant reduction in terminal synaptic branch formation within the postmigratory neurons. These results indicate that while NO-sensitive sGC activity is expressed precociously within the EP cells during their initial migratory dispersal, a role for this signaling pathway can only be demonstrated well after migration is complete, coincident with the formation of mature synaptic connections.

Animals↗
PubMed1998

Attenuation of scopolamine-induced spatial learning impairments by an angiotensin IV analog.

Recently, a receptor for the angiotensin II(3-8) (Ang IV) hexapeptide, was discovered in the hippocampus, suggesting a possible role in learning. The present study utilized intracerebroventricularly (icv) infused scopolamine hydrobromide (scop) to disrupt spatial learning in the circular water maze, followed by the Ang IV analog norleucine1-Ang IV (Nle1-Ang IV), to restore normal performance. Rats were icv pretreated with either scop or artificial cerebrospinal fluid (aCSF) followed by either icv injected Nle1-Ang IV or aCSF, and then behaviourally tested. During acquisition training, each animal's latency to locate the platform, path distance, speed, and efficiency ratios were measured. A probe trial was conducted on the final day of training and the time spent in the target quadrant and the number of crossings over the former location of the platform (annulus crossings) were observed. The results indicate that those animals treated with scop followed by aCSF performed poorly during acquisition training as compared with controls. In contrast, those animals that received scop followed by Nle1-Ang IV attained equivalent latencies, distances, and efficiency ratios to find the platform as those achieved by controls. There were no observed differences in swimming speed, thus arguing against drug-induced motor impairment. During the probe trial, animals treated with scop followed by aCSF spent less time in the target quadrant and made fewer annulus crossings as compared to controls, while the scop, Nle'-Ang IV treated animals performed equivalently to controls. These results suggest that Nle1-Ang IV acts to counteract the disruption of spatial learning induced by scopolamine.

Angiotensin II↗
PubMed1998

Role of nitric oxide in angiotensin IV-induced increases in cerebral blood flow.

The present study investigated the effects of three newly synthesized AngIV analogs (Lysine1-AngIV, Norleucine1-AngIV, and Norleucinal) on cerebral blood flow (CBF) in anesthetized Sprague-Dawley rats utilizing laser-Doppler flowmetry. The results indicate that internal carotid infusions of AngIV, Norleucine1-AngIV, Norleucinal, and Lysine1-AngIV increased CBF above baseline by 25, 32, 33 and 44%, respectively, without changing systemic arterial blood pressure. In a second experiment separate groups of rats were pretreated with nitric oxide (NO) synthase inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) or saline, followed by AngIV or Norleucinal for the purpose of evaluating the hypothesis that the mechanism of action of these compounds is linked to the release of NO. Pretreatment with saline followed by AngIV and Norleucinal increased CBF by 29 and 39%, respectively, while pretreatment with L-NAME blocked the vasodilatory effects of AngIV and Norleucinal, suggesting that the increment in blood flow induced by these compounds is dependent upon the synthesis and release of NO from vascular endothelial cells.

Angiotensin II↗
PubMed1998

Autoradiographic identification of kidney angiotensin IV binding sites and angiotensin IV-induced renal cortical blood flow changes in rats.

The present investigation initially determined that specific binding sites for the hexapeptide angiotensin IV (AngIV) are present in the rat kidney cortex and outer medulla but not in the inner medulla, using in vitro autoradiographic techniques. This binding site has been termed AT4, is distinct from the previously characterized AT1 and AT2 sites, and does not bind the specific AT1 receptor antagonist DuP753 or the AT2 receptor antagonist PD123177. Renal artery infusions of AngIV produced a dose-dependent increase in cortical blood flow without altering systemic blood pressure. In contrast, the infusion of angiotensin II (AngII) induced a dramatic decrease in cortical blood flow, accompanied by a significant elevation in systemic blood pressure. The infusion of [D-Val(1)]AngIV, an analog that does not bind at the AT4 receptor site, and the C-terminal truncated analogs AngIV (1-4) and AngIV (1-5) that possess lower affinity for this site, produced no change in cortical blood flow. The infusion of [Nle1]AngIV and [Lys1]AngIV, analogs that bind with high affinity at the AT4 receptor site, produced increases in cortical blood flow with no influence on blood pressure. Pretreatment with a specific AT4 receptor antagonist, Divalinal-AngIV, completely blocked AngIV-induced elevations in blood flow, but failed to influence AngII-induced decreases in blood flow, suggesting that these ligands are acting at different receptor sites. Pretreatment with the nitric oxide synthase inhibitor, NG-Monomethyl-L-Arginine, also blocked subsequent AngIV-induced increases in cortical blood flow. These data support the notion that AngIV exerts a unique influence upon renal hemodynamics via the AT4 receptor subtype, and suggest that AngIV-induced elevations in blood flow may be mediated by nitric oxide.

Amino Acid Sequence↗
PubMed1998

Effect of long-term olive oil dietary intervention on postprandial triacylglycerol and factor VII metabolism.

Although the beneficial effects of Mediterranean-type diets, which are rich in olive oil, a good source of monounsaturated fatty acids (MUFAs), are generally accepted, little is known about the effects of long-term dietary MUFA intake on postprandial lipoprotein metabolism and hemostasis. This study used a single-blind, randomized, crossover design to investigate the relative effects of a long-term dietary olive oil intervention and a control [saturated fatty acid (SFA)-enriched] diet on postprandial triacylglycerol metabolism and factor VII activity. The postprandial response to a standard test meal was investigated in 23 healthy men who adhered to both diets for 8 wk. cis-MUFAs were successfully substituted for SFAs in the MUFA diet without affecting total dietary fat or energy intakes. The long-term dietary MUFA intervention significantly reduced plasma and LDL-cholesterol concentrations (P = 0.01). Postprandial triacylglycerol concentrations were significantly greater in the early postprandial period after the MUFA diet (P = 0.003). Postprandial factor VII activation and the concentration of the factor VII antigen were significantly lower after the MUFA diet (P = 0.04 and P = 0.006, respectively). This study showed that isoenergetic substitution of MUFAs for SFAs reduces plasma cholesterol and reduces the degree of postprandial factor VII activation. The alterations in the postprandial triacylglycerol response suggest a greater rate of dietary fat absorption and postprandial triacylglycerol metabolism after a diet rich in MUFAs. This study presents new insights into the biochemical basis of the beneficial effects associated with long-term dietary MUFA consumption, which may explain the lower rates of coronary mortality in Mediterranean regions.

Adult↗
PubMed1998

Interpreting the fetal heart rate tracing. Effect of knowledge of neonatal outcome.

OBJECTIVE: To determine if knowledge of neonatal outcome influences obstetricians' retrospective interpretation of fetal heart rate monitor tracings and opinion on the appropriateness of obstetric care. STUDY DESIGN: Ten obstetric case histories that involved a critical judgment by the managing obstetrician were selected for this study. Each case contained a point in the patient's labor at which the physician made a judgment regarding route and timing of delivery. We assembled prenatal history, labor course, delivery, fetal heart rate tracing and neonatal outcome into a concise format. For each case, we created a sham case with identical information and monitor tracing, differing only in having an opposite neonatal outcome. Reviewers were recruited to participate and were unaware of the true intent of the study. Reviewers evaluated tracings for: variability, late decelerations and evidence of hypoxia, and judged whether the decision regarding delivery versus continued labor had been appropriate. Reviewers evaluated the case pairs with one month's time between the true and sham outcome cases. RESULTS: Thirty-six obstetricians reviewed 2 case pairs each for a total of 72 case pairs. When the alleged neonatal outcome was poor, there was a significant tendency to respond that evidence of hypoxia was present (P = .007) or that the obstetrician had made an incorrect decision (P < .001). CONCLUSION: Obstetricians are biased by knowledge of poor neonatal outcome when retrospectively interpreting fetal heart rate tracings and judging appropriateness of obstetric care.

Adult↗
PubMed1997

Important role for angiotensin III and IV in the brain renin-angiotensin system.

Considerable evidence now suggests that the precursors and enzymes necessary for the formation and degradation of biologically active forms of angiotensins are present in brain tissues, accompanied by at least three specific binding sites. It also appears that several forms of angiotensin may serve as signaling agents at these sites. There is accumulating support for the notion that AngII must be converted to AngIII in order to bind at the AT1 and AT2 receptor subtypes, and AngIII must be converted to AngIV in order to activate the AT4 receptor subtype. Further, AngII(1-7) may activate a separate binding site concerned with antidiuresis, however, characterization of this site has not been completed. The AT1 site appears to mediate the classic angiotensin functions concerned with body water balance, maintenance of blood pressure, and cyclicity of reproductive hormones and sexual behaviors. This receptor site also exerts some control over the secretion of pituitary hormones. Less is known about the functional importance of the AT2 site, however, it has been implicated in vascular growth, control of blood flow, and perhaps modulation of NMDA receptors. The AT4 site is heavily distributed in neocortex, hippocampus, cerebellum, and basal ganglia structures, as well as several peripheral tissues. This site appears to mediate memory acquisition and retrieval, the regulation of blood flow, neurite outgrowth, angiogenesis, and kidney function. In addition to the well-studied functions of the brain renin-angiotensin system, additional less well investigated responses are reviewed. These include electrophysiological activation, tachyphylaxis, long term potentiation, learning and memory, and cognitive affect.

Angiotensin II↗
PubMed1997

Angiotensin II- and IV-induced changes in cerebral blood flow. Roles of AT1, AT2, and AT4 receptor subtypes.

Our laboratory has previously reported the discovery of a unique angiotensin binding site (termed AT4) specific for angiotensin IV (AngIV) in cultured vascular endothelial and smooth muscle cells. The present investigation employed laser-Doppler flowmetry to examine the effect of angiotensin II (AngII) and AngIV stimulation of these receptors on cerebral microcirculation in anesthetized Sprague-Dawley rats. Internal carotid artery infusion of AngII at a low dose (0.1 pmol min-1) revealed a 23% reduction in cerebral blood flow (CBF), while the infusion of AngIV increased CBF in a dose-dependent fashion with the highest dose (100 pmol min-1) resulting in an elevation of 30%. In a second experiment separate groups of rats were pre-treated with the AT1 receptor subtype antagonist DuP 753 (Losartan), the AT2 receptor subtype antagonist PD123177, or a newly synthesized AT4 receptor subtype antagonist Divalinal-AngIV (Divalinal), followed by AngII or AngIV for the purpose of determining which angiotensin receptor subtype is responsible for mediating these AngII- and AngIV-induced responses. Pre-treatment with Losartan completely blocked subsequent AngII-induced reductions in CBF, while both PD123177 and Divalinal failed to inhibit this response. In contrast, significant increases in CBF were measured due to AngIV stimulation following pre-treatment with Losartan and PD 123177, while Divalinal abolished this AngIV-induced response. These results suggest that AngII and IV play opposite roles in cerebral microcirculation, i.e., the AT1 receptor subtype mediates AngII-induced reductions in CBF, while the AT4 receptor subtype regulates increases in CBF.

Angiotensin II↗
PubMed1997

An investigation of lower oesophageal redox potentials in gastro-oesophageal reflux patients and healthy volunteers.

Oesophageal electrical properties are thought to be important in the development of gastro-esophageal reflux. This study simultaneously monitored the intraoesophageal pH and redox potentials in 18 patients with gastro-oesophageal reflux symptoms and 15 asymptomatic controls, for a 24 h period. The pH and redox electrodes were positioned 5 cm proximal to the lower oesophageal sphincter, the position of which had been determined by manometry. Since significantly different behaviour was observed during the day and night, the data were divided into periods of waking and sleeping. Data were analysed for acid reflux (pH < 4) and transients in the redox potential-time curve. Both patients and normal subjects showed negative redox transients which were more frequent and pronounced at night than during the day, and which were uncorrelated with acid reflux. The only parameter which was significantly different between normal and refluxing groups was the amount of nocturnal redox activity, which was lower in refluxing subjects than in normals. Some possible hypotheses for these observations, and the origin of the redox species, are discussed.

Adult↗
PubMed1996

Characterization of the binding properties and physiological action of divalinal-angiotensin IV, a putative AT4 receptor antagonist.

Divalinal-Ang IV [V psi (CH2-NH2)YV psi (CH2-NH2)HPF] is being employed increasingly as a specific AT4 antagonist. This use, which necessitates a comprehensive physiological and pharmacological evaluation of Divalinal-Ang IV's functional and receptor binding characteristics in order to ensure its efficacy and specificity, was the stimulus for this study using bovine adrenal membranes. [125I]Ang IV and [125I]Divalinal-Ang IV were shown to bind with high affinity to a similar number of binding sites, suggesting that both bound the same receptor. This notion was verified by competition curves using [125I]Ang IV and [125I]Divalinal-Ang IV that indicated identical rank order affinities for several angiotensin-related peptides and 100% cross-displacement by Ang IV and Divalinal-Ang IV. Furthermore, an autoradiographic comparison of [125I]Ang IV and [125I]Divalinal-Ang IV in 20 microns sections of bovine adrenals revealed near identical binding distributions characterized by heavy binding in the glomerulosa layer and the medulla. Physiological studies in which test compounds were injected into the internal carotid of the rat and cerebral blood flor (CBF) was measured by laser Doppler flowmetry indicated that pretreatment with Divalinal-Ang IV, but not DuP 753 or PD123177, blocked the increased flow observed with Ang IV infusion. Conversely, DuP 753, but not Divalinal-Ang IV or PD123177, inhibited the decrease in flow witnessed with Ang II. Metabolic stability studies utilizing rat kidney homogenates as a peptidase source, demonstrated that the structural changes present in Divalinal-Ang IV greatly increased its resistance to metabolism as compared to Ang IV. Together, these studies show that Divalinal-Ang IV is a stable, efficacious and specific inhibitor of AT4 receptors.

Angiotensin II↗
PubMed1996

The neurochemical and behavioral effects of beta-amyloid peptide(25-35).

Beta-amyloid protein (A beta) fragments have been shown to be neurotoxic and/or enhance neuronal vulnerability when injected into the hippocampus. We investigated alterations in monoamine contents, including norepinephrine (NE), 5-HT and dopamine (DA) in the rat locus coeruleus (LC) one week following the injection of beta-amyloid peptide fragment 25-35 (beta (25-35)) into the left dorsal hippocampal areas CA1-3. A single treatment of beta (25-35) had no effect on any monoamine levels. Rats that received two treatments (separated by 7 days) revealed significant elevations in NE, 5-HT, and 5-HIAA as compared with the control group injected with ddH2O. However, these changes were observed in the LC on the contralateral side, whereas the injected side exhibited no significant change. These effects may result from an enhanced synthesis of NE by the contralateral LC neurons to compensate for the loss of tyrosine hydroxylase and accompanying recurrent inhibition in a small number of their population. In a second experiment, the influence of beta (25-35) on spatial learning was evaluated using a Morris water maze task. Rats received bilateral injections of beta (25-35) into hippocampal areas CA1-3. The results indicate that beta (25-35)-treated rats exhibited significantly longer latencies and swim distances to locate the submerged platform than did members of the control group.

Amyloid beta-Peptides↗
PubMed1996

Effects of LY231617 and angiotensin IV on ischemia-induced deficits in circular water maze and passive avoidance performance in rats.

The antioxidant LY231617 has previously been shown to offer significant protection against postischemic cell death in the hippocampus and corpus striatum of rats. The present results extend this observation by demonstrating a concomitant protection against the spatial memory deficits that accompany damage to the hippocampus, as measured by the circular water maze task. These animals were further tested for changes in associative memory by employing a passive avoidance conditioning task. No deficits in passive avoidance conditioning were measured among the 4-vessel occlusion animals treated with LY231617 or vehicle. However, the intracerebroventricular injection of angiotensin IV (Ang IV) immediately prior to foot-shock conditioning improved retention of the conditioned response during the subsequent 2-day period. These results suggest that LY231617 can offer considerable protection against global ischemia-induced cell death in the hippocampus with resulting preservation of spatial memory abilities. In addition, untreated animals that suffered cell losses in the hippocampus remained capable of responding to the facilitory effect of centrally administered Ang IV on a non-spatial memory task. The hypothesized mechanisms of the protection characteristics of LY231617, and the nootropic effect of Ang IV, are discussed.

Angiotensin II↗