Sodium appetite in adult rats following ω-3 polyunsaturated fatty acid deficiency in early development.

We examined the effect of ω-3 polyunsaturated fatty acid (PUFA) deficiency during development on sodium appetite. Being raised on an ω-3 PUFA deficient diet increased the intake of 0.5M NaCl following furosemide-induced sodium depletion by 40%. This occurred regardless of the diet they were maintained on later in life, and the increased consumption persisted for 3 days. In a second study, animals were administered furosemide and low-dose captopril. Sodium consumption of deficient raised animals was again higher than that of the control raised. Fos immunoreactivity in brain areas associated with sodium appetite and excretion were not influenced by diet. Our findings indicate that inadequate dietary ω-3 PUFA during development results in an exaggerated sodium appetite later in life.

Selective reduction in body fat mass and plasma leptin induced by angiotensin-converting enzyme inhibition in rats.

OBJECTIVE: There is emerging evidence that angiotensin stimulates adipocyte differentiation and lipogenesis. This study tested the hypothesis that inhibition of angiotensin II by treatment with an angiotensin-converting enzyme inhibitor, perindopril, would reduce fat mass in rats. DESIGN: After a 12-day baseline, rats were divided into two groups: one was untreated and the other received perindopril (1.2 mg kg(-1) per day) in drinking water for 26 days. SUBJECTS: In total, 16 male Sprague-Dawley rats aged 10 weeks at the start of the study. MEASUREMENTS: Plasma leptin was measured in samples collected at baseline, half-way through and at the end of treatment. Body weight, food and water intake were measured daily throughout the experiment. Body fat mass, bone and lean mass were determined by dual energy X-ray absorptiometry (DEXA) at the end of the treatment period. RESULTS: Daily food intake was the same in both groups throughout the study. By the end of treatment, animals receiving perindopril showed a modest reduction in weight gain relative to the untreated animals (62.4+/-5.0 g vs 73.0+/-4.0 g; P<0.05). DEXA analysis showed that body composition was greatly altered and the perindopril-treated group had 26% less body fat mass than the untreated group (61.0+/-5.2 g vs 44.4+/-4.2 g; P<0.01). The reduction in body fat mass was correlated with reductions in the weight of both the epididymal and retroperitoneal fat pads (P<0.001). Similarly, plasma leptin was reduced by perindopril treatment (4.64+/-0.56 ng ml(-1)) compared to the untreated group (8.27+/-1.03 ng ml(-1); P<0.001). In contrast, there were no differences in lean or bone mass between the two groups. CONCLUSION: Oral treatment with perindopril selectively reduced body fat mass without influencing daily food intake. In contrast, there were no differences in lean or bone mass between the two groups.

Omega-3 polyunsaturated fatty acid supplementation reduces hypertension in TGR(mRen-2)27 rats.

To establish the effect of dietary omega-3 PUFA on angiotensin II (ANG II)-mediated hypertension, male TGR (mRen-2)27 (Ren-2) rats (animals with high ANG II activity) were maintained on a diet either deficient or sufficient in omega-3 PUFA from conception. Half the animals on each diet were treated with the angiotensin-converting enzyme inhibitor, perindopril, from birth. Ren-2 rats fed the omega-3 PUFA deficient diet were significantly more hypertensive than those fed the omega-3 PUFA sufficient diet. Perindopril reduced the blood pressure of both omega-3 PUFA-deficient and omega-3 PUFA-sufficient diet-fed Ren-2 rats. Body weight, body fat and plasma leptin were reduced by perindopril treatment but not affected by omega-3 PUFA supply. Given that the elevated blood pressure of the Ren-2 rat is mediated by ANG II, the data suggest that omega-3 PUFA may reduce hypertension via the renin-angiotensin system.

Cardiovascular effects of long-term central and peripheral administration of urocortin, corticotropin-releasing factor, and adrenocorticotropin in sheep.

The neuroendocrine hormones ACTH and corticotropin- releasing factor (CRF), which are involved in the stress response, have acute effects on arterial pressure. New evidence indicates that urocortin (UCN), the putative agonist for the CRF type 2 receptor, has selective cardiovascular actions. The responses to long-term infusions of these hormones, both peripherally and centrally, in conscious animals have not been studied. Knowledge of the long-term effects is important because they may differ considerably from their acute actions, and stress is frequently a chronic stimulus. The present experiments investigated the cardiovascular effects of CRF, UCN, and ACTH in conscious sheep. Infusions were made either into the lateral cerebral ventricles (i.c.v.) or i.v. over 4 d at 5 microg/h. UCN infused i.c.v. or i.v. caused a prolonged increase in heart rate (HR) (P < 0.01) and a small increase in mean arterial pressure (MAP) (P < 0.05). CRF infused i.c.v. or i.v. progressively increased MAP (P < 0.05) but had no effect on HR. Central administration of ACTH had no effect, whereas systemic infusion increased MAP and HR (P < 0.001). In conclusion, long-term administration of these three peptides associated with the stress response had prolonged, selective cardiovascular actions. The striking finding was the large and sustained increase in HR with i.c.v. and i.v. infusions of UCN. These responses are probably mediated by CRF type 2 receptors because they were not reproduced by infusions of CRF.

The role of docosahexaenoic acid in retinal function.

An important role for docosahexaenoic acid (DHA) within the retina is suggested by its high levels and active conservation in this tissue. Animals raised on n-3-deficient diets have large reductions in retinal DHA levels that are associated with altered retinal function as assessed by the electroretinogram (ERG). Despite two decades of research in this field, little is known about the mechanisms underlying altered retinal function in n-3-deficient animals. The focus of this review is on recent research that has sought to elucidate the role of DHA in retinal function, particularly within the rod photoreceptor outer segments where DHA is found at its highest concentration. An overview is also given of human infant studies that have examined whether a neonatal dietary supply of DHA is required for the normal development of retinal function.

Sorsby's fundus dystrophy.

BACKGROUND: Sorsby's fundus dystrophy describes the condition in which an autosomal-dominant inherited macular dystrophy with bilateral central visual loss is accompanied by progressive atrophy of the peripheral choroid and, subsequently, the outer retina. The first symptom of this condition is nyctalopia, whereas (typically) the first sign is the appearance of white-yellow deposits in the posterior pole. CASE REPORT: We report a case of Sorsby's fundus dystrophy, manifested with central visual loss in the fifth decade of life. A battery of tests--including ophthalmoscopy, electroretinography, color vision, Pelli-Robson contrast sensitivity, and fluorescein angiography--were used to evaluate the condition. CONCLUSIONS: While advances in understanding the etiology of Sorsby's fundus dystrophy have been made, the condition remains difficult to treat and the outcome is often devastating. The benefits of various methods of treatment, such as laser photocoagulation and dietary supplementation are unclear Patients affected by this condition should be managed in a manner similar to that for end-stage sufferers of age-related macular degeneration.

Pseudoduplication of the optic nerve head.

BACKGROUND: Pseudo-doubling of the optic nerve head is a spectacular clinical entity, in which a lesion resembling an optic disk appears adjacent to the true optic disk. CASE REPORT: A case of unilateral pseudo-doubling of the optic disk with bilateral optic nerve pits is presented. CONCLUSIONS: The lesion is congenital, and represents a chorioretinal coloboma with optic disk involvement. Pseudo-doubling can be differentiated from true doubling of the optic nerve by the imaging techniques of ultrasonography, computerized tomography, and magnetic resonance imaging.

Effects of dietary n-3 fatty acid deficiency and repletion in the guinea pig retina.

PURPOSE: To investigate the nature and reversibility of biochemical and functional changes in the retina encountered over a single generation of dietary n-3 polyunsaturated fatty acid deficiency in guinea pigs. METHODS: Dunkin-Hartley guinea pigs were fed for 16 weeks after weaning with diets supplemented with safflower seed oil (n-3 deficient) or canola oil (n-3 sufficient, control). A number of deficient animals were repleted at 6 weeks with canola oil for 5 or 10 weeks, or at 11 weeks for 5 weeks. Electroretinograms (0.8 and 4.3 log scot td x sec) were collected at 6, 11, and 16 weeks after weaning. Conventional waveforms (a- and b-waves), oscillatory potentials, and receptoral and postreceptoral subcomponents (PIII and PII, respectively) were evaluated. Cone pathway function was assessed with 30-Hz flicker at the brighter intensity. Retinal phospholipid fatty acids were measured by capillary gas-liquid chromatography. RESULTS: Electroretinographic amplitudes showed statistically significant losses in b- and a-waves after 6 and 16 weeks of dietary n-3 deficiency, respectively. The response amplitude to 30-Hz flicker was reduced 42% after 16 weeks. Retinal docosahexaenoic acid (DHA) levels of animals maintained on the safflower oil diet for 16 weeks were 42% of levels in age-matched control subjects. There were significant losses in maximum response amplitudes (R(mPIII) and R(mPII)), although the major effect was a reduction in sensitivity of the receptoral response. Complete functional recovery was observed only in animals repleted for 10 weeks. CONCLUSIONS: Functional deficits in PIII and PII of the electroretinogram were apparent in first-generation guinea pigs fed an n-3 deficient diet. These losses showed a correlation with age and retinal DHA level, although varying degrees of dependence on the DHA level were found. All functional deficits were reversed after 10 weeks of dietary n-3 repletion. The results suggest that DHA may serve several functional and structural roles in the retina and further emphasize the requirement for DHA in the normal development of vision.

Effect of diet on the rate of depletion of n-3 fatty acids in the retina of the guinea pig.

This study has assessed the influence of maternal n-3 long chain polyunsaturated fatty acid supply and dietary manipulation after weaning on the retinal polyunsaturated fatty acid profile. Infant guinea pigs born of dams fed one of two commercial chow diets (differing in the amount of eicosapentaenoic, docosapentaenoic, and docosahexaenoic acids) were raised in two separate experiments, and subsequently partitioned into two diet groups, one supplied with a high level of alpha-linolenic acid (canola oil supplemented), the other with a very low level of alpha-linolenic acid (safflower oil supplemented). Guinea pigs born of dams supplied with the longer chain n-3 fatty acids in the commercial pellets (experiment 2) showed higher levels of retinal docosahexaenoic acid at weaning compared with those born to dams fed chow containing only alpha-linolenic acid (experiment 1). The rate of depletion of retinal docosahexaenoic acid after weaning onto the safflower oil diet was described by a two-stage exponential decay, possibly reflecting systemic and local conservation mechanisms, in conditions of dietary n-3 fatty acid deprivation. The rate of docosahexaenoic acid depletion in the group with the lower retinal docosahexaenoic acid at weaning was more than double the rate of depletion in the group with the higher weaning docosahexaenoic acid value. The endpoint retinal docosahexaenoic acid level at 16 weeks post-weaning after dietary n-3 fatty acid depletion on the safflower oil diet in the group, which started with the lower retinal docosahexaenoic acid level, was approximately half that compared with the group from the dams fed long chain n-3 fatty acids (experiment 1, 5% (interpolated), experiment 2, 9%). These results suggest that an adequately supplied mother is capable of providing an infant with enough n-3 fatty acids to withstand a longer period of dietary deprivation imposed after weaning.

Comparison of guinea pig electroretinograms measured with bipolar corneal and unipolar intravitreal electrodes.

This study considers the precision and accuracy of bipolar corneal electrodes compared with unipolar intravitreal methods in collecting electroretinographic (ERG) recordings from a small animal. Flash ERGs were obtained from 9 adult guinea pigs on three occasions. Corneal bipolar (Burian-Allen) electrodes were used to collect data on the first two occasions whereas unipolar intravitreal electrodes were used on the last. We identified the a-wave, b-wave, oscillatory potentials, PIII and PII responses. Intensity-response functions were fit using a Naka-Rushton relationship with a bootstrap estimating the 95% confidence limits. Discrepancy analysis was applied to determine the coefficient of agreement. We found significantly larger amplitudes with unipolar intravitreal electrodes (ANOVA; a-wave, p<0.002; b-wave, p<0.001; Oscillatory potentials (OPs), p<0.005) especially at high intensities. Implicit times showed little differences between electrodes for the a-wave, significantly faster (p<0.03) b-waves at some intensities, and significantly slower (p<0.005) OP implicit times across all intensities. The PIlI amplitude (log microV), sensitivity and timing were not significantly different (p>O.05) if expressed in logarithmic units but PII amplitude (log microV) was significantly smaller with corneal electrodes. We suggest that a conversion factor (x1.35) should be applied to data collected with bipolar corneal electrodes to estimate the amplitudes of the modelled parameters accurately. The corneal electrode gave a precision of +/-39 microV which yields a statistical power of 0.90 for a sample size of 7 subjects. We conclude that bipolar corneal electrodes provide smaller electroretinogram amplitudes due to their location and reduced span of the retinal generators.

Effect of dietary n-3 deficiency on the electroretinogram in the guinea pig.

Despite the abundance of n-3 polyunsaturated fatty acids, particularly docosahexaenoic acid (DHA), in the retina of all mammals, their role in vision remains unclear. However, the widely accepted notion that DHA is universally important in the retinal function was questioned in an earlier study (see text) involving guinea pigs, completely depleted of retinal DHA. The purpose of this study was to replicate this mammalian model of such deficiency and to determine any abnormalities in the electroretinogram. Guinea pigs were raised through three generations on 1 of 2 semipurified diets, containing different amounts of n-3 fatty acids, as determined by the supplementary oil which was the sole source of lipid in each diet. The added oils were safflower oil (n-6/n-3 = 72.0) or canola oil (n-6/n-3 = 2.5). Comprehensive electroretinographic assessment was conducted on guinea pigs, aged 6-9 weeks (safflower n = 13, canola n = 12), and retinae were extracted and the phospholipid fatty acid profile analyzed. Phospholipid fatty acid analysis revealed significant DHA deficiency (p < 0.001) in guinea pigs reared on the safflower oil diet (retinal DHA 2.5%) as compared with the canola oil group (retinal DHA 21.0%). Analysis of the electroretinogram showed significant reductions (p < 0.003) in both peak-to-peak and a-waves of safflower oil fed animals.

The effect of docosahexaenoic acid on the electroretinogram of the guinea pig.

Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid, is found in consistently high concentrations in the retinae of mammals, yet its role in vision remains unclear. In this study, a mammalian model of variable retinal DHA concentration has been developed, such that the retinal phospholipids of guinea pigs contained between 2.5 and 30.8% DHA. Visual function was assessed using full-field flash electroretinography, over a range of exposure levels spanning six log units. Trend analysis indicated that retinal function was altered by the tissue DHA level, and was described by a second-order polynomial "inverted U-shaped" function. The results suggested that although some amount of DHA is essential for normal retinal function, increases in the DHA level past an optimal amount, found to be 19%, provided diminishing returns. In this study, manipulation of the retinal DHA level accounted for 21-35% of the electroretinographic variability.

Dietary manipulation of long-chain polyunsaturated fatty acids in the retina and brain of guinea pigs.

High levels of n-6 docosapentaenoic acid (22:5n-6) have been reported in the retina of guinea pigs fed commercially-prepared gain-based rations (commercial diet). In rats and monkeys, high levels of 22:5n-6 are an indicator of n-3 polyunsaturated fatty acid (PUFA) deficiency. We have examined the fatty acid composition of the retina and brain in guinea pigs fed a commercial diet or one of three semi-purified diets containing three different levels of n-3 PUFA. The diets comprised a diet deficient in n-3 PUFA (semi-purified diet containing safflower oil), two diets containing alpha-linolenic acid (standard commercial laboratory diet and semi-purified diet containing canola oil), and a diet containing alpha-linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid (DHA) (semi-purified diet containing canola oil, safflower oil, and fish oil). Two groups of guinea pigs were given the diets from day 1 to 4 wk or day 1 to 8 wk, when they were sacrificed and the retinal tissues were extracted and analyzed for PUFA content by gas-liquid chromatography. Fatty acid analyses of the retinal phospholipids of the four-week-old animals revealed that the group fed DHA (from the fish oil) had the highest level of DHA (32%), compared with values of 19 and 13% for the groups fed canola oil diet and commercial diet, respectively, and 2% for the group fed the diet deficient in n-3 PUFA.(ABSTRACT TRUNCATED AT 250 WORDS)