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Biomedical subjects

K D Croft

Publications and source records attributed to K D Croft.

At least 73 records · Page 4Linked to original sources
PubMed1988

The effect of dietary fish oil and long-term salt loading on blood pressure and eicosanoid metabolism in spontaneously hypertensive rats.

1. Dietary suppression of prostanoid synthesis with fish oils has had little effect on blood pressure in models of experimental hypertension in rats. However, a pressor effect of dietary fish oils was observed in spontaneously hypertensive rats (SHR) subject to 1 week of salt loading. 2. Animals were allocated to semisynthetic diets containing either 10% by weight Max EPA fish oil or a control diet of coconut oil, and studied after receiving 1.5% saline for 4 weeks. 3. Within the first week of salt loading, SHR-fed fish oil showed an increase in blood pressure (mean = 9 mmHg) relative to controls. This effect was transient, and after the first week of salt loading there was little difference in blood pressure between the two dietary groups. 4. Following dietary treatment there were substantial changes in plasma fatty acid composition with a 48% decrease in arachidonic acid content of fish oil-fed rats compared with control animals. Rats on the fish oil diet showed a threefold decrease in serum thromboxane generation. Prostacyclin production by incubated segments of aorta was reduced by more than 50% compared with the coconut oil-fed control group. 5. SHR on the fish oil diet showed increased urine volume and sodium excretion, presumably due to increased fluid and salt intake. 6. This study shows that dietary suppression of prostacyclin synthesis is associated with only a minor effect on blood pressure in long-term salt loading of SHR.

6-Ketoprostaglandin F1 alpha↗
PubMed1988

Effect of dietary fish oils on the formation of leukotriene B4 and B5, thromboxane and platelet activating factor by rat leukocytes.

1. This study investigates the effect of dietary eicosapentaenoic acid (EPA), in the form of 'Max EPA' fish oil, on leukotriene B4 (LTB4) production in ionophore-stimulated rat leukocytes. Male Wistar rats (200-250 g) were fed for 3 weeks on a synthetic chow supplemented with either 10% by weight Max EPA oil or a coconut oil/safflower oil mixture. 2. The EPA-rich diet significantly increased the EPA content of leukocyte phospholipids and decreased the arachidonic acid level by 35% (P less than 0.001) compared with the control diet. 3. The concentration of leukotrienes in the ionophore (A23187) stimulated leukocytes was measured by reverse-phase HPLC using prostaglandin B2 as the internal standard. The EPA-supplemented diet caused a 50% decrease in LTB4 production (P less than 0.001) and a concomitant increase in the formation of the biologically less active LTB5 compared with the control diet. The amount of LTB4 and LTB5 produced by stimulated leukocytes closely resembled the changes in arachidonic acid and EPA content of leukocyte phospholipids. 4. Thromboxane B2 (TxB2) production in stimulated leukocytes from the EPA-fed animals was also decreased compared with the control group. 5. Although the formation of platelet activating factor by stimulated leukocytes was not altered by dietary treatment, the ability of an EPA-rich diet to decrease LTB4 and TxB2 production suggests that these diets may attenuate leukocyte activity and have useful anti-inflammatory effects.

Animals↗
PubMed1987

The effect of vitreous humour on prostaglandin production by cultured rabbit chorioretinal fibroblasts.

Factors in vitreous humour which regulate prostaglandin production were investigated using cultured rabbit chorioretinal fibroblasts. These cells produced predominantly prostaglandin E2, 6-ketoprostaglandin F1 alpha, a compound likely to be a metabolite of prostaglandin E2 and 5-hydroxyeicosatetraenoic acid. The synthesis of 6-ketoprostaglandin F1 alpha was nearly completely inhibited by the cyclooxygenase inhibitor aspirin and partially inhibited by 10(-6) M dexamethasone (49%) and 10(-5) M forskolin (68%). Addition of 10% rabbit vitreous humour to subconfluent cells maintained in Dulbecco's modified Eagle's medium plus 1% fetal bovine serum resulted in stimulation of 6-ketoprostaglandin F1 alpha production by as much as 246% as measured by radioimmunoassay. Chorioretinal fibroblasts labelled by [3H]arachidonic acid incorporation into cellular phospholipids synthesised greater amounts of all labelled arachidonic acid metabolites in response to vitreous humour. It was concluded, therefore, that there are factors present in vitreous humour of molecular weight above 10 kDa which are capable of stimulating cellular cyclooxygenase activity. Confluent cells also responded to a factor(s) present in vitreous humour. The fraction of less than 10 kDa inhibited 6-ketoprostaglandin F1 alpha production by 50% when used at a concentration of 10%. Furthermore, 6-ketoprostaglandin F1 alpha production in confluent cells (but not subconfluent cells) was inhibited to 40% of control levels by vitamin C at a concentration of 1 mg/100 ml. The latter result points to an inhibitory role for vitamin C in vitreous humour. We conclude, therefore, that vitreous humour contains factors important for the regulation of prostaglandin metabolism in the eye.

Animals↗
PubMed1987

Differential inhibition of thromboxane B2 and leukotriene B4 biosynthesis by two naturally occurring acetylenic fatty acids.

The seed oil of the plant Ixiolaena brevicompta is a rich source of crepenynic acid (octadec-cis-9-en-12-ynoic acid), which has been linked with extensive sheep mortalities in Western New South Wales and Queensland, Australia. A number of acetylenic fatty acids have been found to interfere with lipid and fatty acid metabolism and inhibit cyclooxygenase and lipoxygenase enzymes in a variety of tissues. We have investigated the effects of crepenynic acid and ximenynic acid (octadec-trans-11-en-9-ynoic acid) on leukotriene B4 and thromboxane B2 production in rat peritoneal leukocytes and compare them with non-acetylenic compounds linoleic and ricinoleic acids. In concentrations ranging from 10 to 100 microM linoleic acid and ricinoleic acid had only minimal effects on leukotriene B4 and thromboxane B2 production in ionophore-stimulated cells. Ximenynic acid gave dose-dependent inhibition of leukotriene B4, thromboxane B2 and 6-ketoprostaglandin F1 alpha production. Ximenynic acid appears to be a more effective inhibitor of leukotriene B4 than crepenynic acid with an IC50 of 60 microM compared to 85 microM. On the other hand, crepenynic acid is a much more effective inhibitor of the cyclooxygenase products, having an IC50 for thromboxane B2 of less than 10 microM. Both acetylenic fatty acids inhibited phospholipase activity in these cells by 40-50% at a concentration of 100 microM but had no inhibitory effect at 10 microM. These results indicate that crepenynic acid and ximenynic acid differentially inhibit the cyclooxygenase and lipoxygenase products of stimulated leukocytes, and that at high doses of these fatty acids the effect on these products may be partially due to inhibition of phospholipase A2.

Alkynes↗
PubMed1987

The effect of dietary eicosapentaenoic acid on arachidonic acid incorporation and metabolism in rat leukocytes.

Arachidonic Acid (AA) released from membrane phospholipids by phospholipase A2 during cell activation is the major polyunsaturated fatty acid precursor in mammals for the cyclooxygenase and lipoxygenase pathways. Eicosapentaenoic acid (EPA), a major polyunsaturated fatty acid in fish oils competes with AA for these enzymes. The resulting products from EPA are generally less potent than the corresponding AA metabolites which may explain the beneficial effects of this oil in reducing thrombotic and inflammatory responses. This study compares the incorporation of 14C-AA into leukocyte phospholipids and its release and metabolism by the cyclooxygenase and lipoxygenase pathways in rats fed a 'Max EPA' fish oil rich diet (EPA group) and a hydrogenated coconut/safflower oil control diet. More than 75% of radiolabel was incorporated into leukocytes with no difference seen between dietary groups. Upon stimulation with calcium ionophore, the EPA group released significantly more radiolabelled AA than the control group. The EPA diet showed a significant increase in the formation of 5-hydroxyeicosatetraenoic acid and 6-keto-prostaglandin F1 alpha but no difference was seen in leukotriene B4 formation. The majority of radiolabel released was free AA, this being significantly higher in the EPA group than in the control. The percentage of radiolabel remaining after stimulation in phosphatidylglycerol, phosphatidylethanolamine and neutral lipids was significantly less in EPA fed rats. As the release and metabolism of endogenous AA may not be the same as 14C-AA, these results do not necessarily indicate that the mass of AA available for eicosanoid biosynthesis has been altered by the EPA diet.

Animals↗
PubMed1987

The effect of dietary fish oil and salt on blood pressure and eicosanoid metabolism of spontaneously hypertensive rats.

This study was designed to investigate the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats under conditions of normal and elevated salt intake. Forty rats from both strains were placed on either a two-series PG inhibitory diet of Max eicosapentaenoic acid (EPA) fish oil or a control diet of saturated fat for an initial period of 4 weeks. The groups were then divided into two, so that half of each received 1.5% saline in place of their drinking water for 1 week. Blood pressure of the SHR and WKY were unaffected by dietary fat before the addition of saline, but with salt loading, the Max EPA-fed SHRs showed a mean blood pressure increase of 21 mmHg relative to the EPA-fed SHR with access to water. Rats fed EPA showed impaired ability to generate serum thromboxane (TXB2) and in the groups with access to water, diminished excretion of urinary 6-keto-PGF1 alpha and PGE2. Salt loading increased prostanoid synthesis and excretion. Spontaneously hypertensive rats had greater serum TXB2 generating capacity than WKYs, but diminished urinary PGE2 excretion in those animals with access to water. The increased blood pressure observed in the salt-loaded SHR on the Max EPA-diet may be explained by reduced PG synthesis resulting in either mild sodium retention and/or increased vascular reactivity.

Animals↗
PubMed1987

Dietary suppression of prostaglandin synthesis does not accelerate DOCA/salt hypertension in rats.

1. This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in DOCA/salt-treated rats. 2. After an initial 4 week period on either a 2-series PG 'inhibitory' diet of fish oil (Max EPA), A 'stimulatory' diet of safflower oil or a control diet of saturated fat, three groups of rats were placed on a DOCA/salt regimen for a further 4 weeks. Another group on the saturated fat diet continued their diet without DOCA/salt administration. 3. All the DOCA-treated groups showed a marked increase in blood pressure. However, both polyunsaturated fat (PUFA)-fed groups had blood pressures significantly lower then the saturated fat control. 4. Rats on the Max EPA showed impaired ability to generate prostanoids in vitro (serum, aorta and kidney) and in vivo (urinary PG excretion). DOCA administration increased urinary PGE2 excretion. 5. Thus, dietary suppression of 2-series PG is not accompanied by accelerated DOCA/salt hypertension. The reduction in blood pressure observed in both the safflower and Max EPA-fed groups may be due to PUFA-induced changes in cell membrane fluidity.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Dietary fish oils reduce plasma levels of platelet activating factor precursor (lyso-PAF) in rats.

The object of this study was to develop an assay for platelet activating factor (PAF) in rat plasma, and to utilise this to determine the effects of dietary fish oil on PAF in normotensive and spontaneously hypertensive rats. Measurement of platelet activating factor in blood plasma has proved difficult because of its rapid hydrolysis in vivo to lyso PAF. We describe here a method based on the prior acetylation of lyso PAF extracted from plasma to PAF before bioassay using 14C-serotonin labelled platelets. The active material found in acetylated plasma extracts was characterized as PAF by its chromatographic mobility, the action of phospholipases A2, C and D and by cross-desensitization studies with rabbit platelets. Rats fed dietary fish oil ('max EPA') had significantly decreased plasma lyso-PAF levels compared to control animals fed hydrogenated coconut oil (HCO). Serum thromboxane B2 (TXB2) levels were also significantly lower in animals fed the 'max EPA' diet. Spontaneously hypertensive rats (SHR) had significantly lower plasma lyso-PAF levels than their normotensive Wistar Kyoto (WKY) controls maintained on the same diets. It is proposed that dietary alterations in PAF synthesis may influence platelet behaviour in addition to the well described effects of dietary fish oil on the proaggregatory prostanoid TXA2. Rat strain differences in lyso-PAF synthesis occur, but are unlikely to be related to the maintenance of hypertension in SHR.

Animals↗
PubMed1986

Effect of salt loading on blood pressure and eicosanoid metabolism of spontaneously hypertensive rats fed a fish oil enriched diet.

This study investigated the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats under conditions of normal and elevated salt intake. After an initial period of 4 weeks on either a 2-series PG 'inhibitory' diet of fish oil (maxEPA) or a control diet of saturated fat, half of each group received 1.5% saline for 1 week. Blood pressures were unaffected by diet during the period of normal salt intake, but following salt loading, the maxEPA-fed SHR showed a blood pressure increase (mean = 21 mmHg) relative to the EPA-fed rats on water. Rats on maxEPA showed impaired ability to generate serum thromboxane and diminished excretion of urinary 6-keto-PGF1 alpha and PGE2. SHR on water showed greater serum TXB2 generating capacity than WKY, but diminished urinary PGE2 excretion. Thus, the increased blood pressure observed in the salt-loaded SHR on the maxEPA diet may be explained by reduced renal PG synthesis resulting in either mild sodium retention and/or increased vascular reactivity.

Animals↗
PubMed1986

Increased aortic PGI2 and plasma lyso-PAF in the unclipped one-kidney hypertensive rat.

Previous studies have implicated vasodilatory prostaglandins (PGs) in the reversal of hypertension following unclipping in the one-kidney, one-clip (1K,1C) hypertensive rat. The capacity of the aorta to synthesize prostacyclin (PGI2) was compared in clipped (group A, n = 9), unclipped (group B, n = 8 and group D, n = 9), and sham-unclipped (group C, n = 9) 1K,1C hypertensive rats. The involvement of platelet-activating factor (PAF), a potent renal antihypertensive phospholipid, in the reversal of renal clip hypertension was also examined. Hypertensive rats [systolic blood pressure (BP) greater than 180 mmHg] were fed a synthetic diet for 4 wk, after which group A was killed immediately, group C was sham-unclipped, and groups B and D unclipped and killed 24 h later. Blood was drawn for the measurement of plasma lyso-PAF (the precursor of PAF) and the aorta removed for determination of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha, the stable hydrolysis product of PGI2). BP fell substantially in the unclipped rats (groups B and D) but did not change in the sham-unclipped rats (group C). Mean aortic 6-keto-PGF1 alpha was increased in the unclipped groups [group B, 15.4 +/- 2.4 (SE) ng/mg; group D, 10.8 +/- 2 ng/mg] compared with group A (7.7 +/- 1 ng/mg) and group C (7.1 +/- 1 ng/mg) (H = 13.74, P less than 0.01). Plasma lyso-PAF was also significantly increased in the unclipped (group D, 261 +/- 26 ng/ml) vs. the sham-unclipped group (group C, 211 +/- 23 ng/ml, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Onset of changes in phospholipid fatty acid composition and prostaglandin synthesis following dietary manipulation with n-6 and n-3 fatty acids in the rat.

A synthetic diet preparation supplemented with 10% by weight of either safflower oil, hydrogenated coconut oil containing 3% safflower oil, or 'max EPA' fish oil was fed to rats over a 8-week period. Serial measurements of serum fatty acids, serum thromboxane B2 and urinary prostaglandin excretion were taken during the treatment period to assess the rate of change in fatty acid composition and prostaglandin synthesis following dietary manipulation. There was no significant change in weight gain between the dietary groups during the treatment period. Significant changes in serum fatty acids occurred within 48 h of treatment, with the 'max EPA' oil group having arachidonic acid levels reduced by 23% (P less than 0.01) compared to the coconut oil group. Conversely, rats fed safflower oil had an 18% enhancement of arachidonic acid during the same time period. Whole blood synthesis of thromboxane B2 was significantly depressed (P less than 0.01) after 48 h in rats fed 'max EPA' oil compared to the safflower oil or coconut oil groups. This suppression reached a maximum of 65% (P less than 0.001) after 7 days of dietary 'max EPA' oil treatment. The safflower oil and coconut oil-fed groups showed the same levels of serum thromboxane B2 production over the treatment period. Urinary excretion of both 6-ketoprostaglandin F1 alpha and prostaglandin E2 varied significantly (P less than 0.01) between the groups after 7 days of dietary treatment. Rats fed 'max EPA' oil had depressed urinary prostanoid excretion compared to the safflower and coconut oil groups which remained very similar to each other. After the 8-week treatment period rats were killed and the phospholipid fatty acid composition and prostaglandin-generating capacity of platelets, aorta and renal tissue was examined. Prostanoid production by kidney cortex and medulla and segments of aorta was consistently suppressed in rats fed 'max EPA' oil. These observations correlated well with changes in the phospholipid fatty acid profiles in these tissues. This study shows rapid changes in serum fatty acids and thromboxane B2 generation following dietary manipulation, while changes in urinary excretion or prostanoid metabolites occur only after a longer time period.

Animals↗
PubMed1985

Study of diet and drug interactions on prostanoid metabolism.

To study the extent to which combinations of different dietary lipids stimulate or inhibit prostanoid synthesis groups of 12 rats were fed diets containing 10% (w/w) of either safflower oil, hydrogenated coconut oil/safflower oil, cod liver oil/safflower oil or cod liver oil/linseed oil for a period of four weeks. All diets, with the exception of the safflower oil feed, contained similar levels of linoleic acid. Two further groups of rats placed on the cod liver oil diets were injected with indomethacin (4 mg/kg, i.p.) every three days to establish the completeness of dietary prostaglandin (PG) inhibition. In spite of a 20 fold difference in dietary linoleic acid content, the safflower oil group had similar PG generating capacities to the saturated fat control group, suggesting tight metabolic control of PGs and their precursors. Although there were prostanoid variations in tissue responses, both of the cod liver oil diets substantially reduced generation of aortic, whole blood and renal prostanoids, and decreased urinary PG excretion. The degree of inhibition of renal PGs was substantially greater in the cod liver oil/linseed oil group, with prostaglandin levels being 35% lower than those observed in the cod liver oil/safflower oil fed animals suggesting that linolenic acid and the marine oil fatty acids act synergistically to inhibit formation of 2-series prostaglandins. Concurrent administration of omega-3 fatty acids and indomethacin reduced PG levels further than those obtainable by diet alone, demonstrating that the diets did not result in maximal inhibition. Awareness of these various effects is important for both physiological or clinical studies in which dietary manipulations are used as a means of modifying prostanoid synthesis.

Animals↗
PubMed1985

Blood pressure and dietary polyunsaturated and saturated fats: a controlled trial.

Fifty-four healthy, omnivore normotensive volunteers aged 20-59 years were randomly allocated either to a control group eating a low polyunsaturated to saturated fat ratio (P/S ratio) diet (0.3) throughout, or to one of two experimental groups eating a high P/S ratio diet (1.0) for one of two 6-week experimental periods. Changes in other components were avoided. Twenty-four hour diet records showed substantial changes in the P/S ratio for experimental groups when on the high P/S ratio diet (0.3 to 1.0). There were significant increases in relative concentrations of linoleic acid in plasma phospholipids when on the high P/S ratio diet. There was no consistent effect of dietary P/S ratio elevation from 0.3 to 1.0 on group mean systolic and diastolic blood pressures. Adjustment of blood pressure changes for changes in electrolytes, other dietary components, plasma lipids, weight and other lifestyle variables did not alter this result. It was concluded that the blood pressure lowering effect of a vegetarian diet reported previously was unlikely to have been due to changes in dietary P/S ratio.

Adult↗
PubMed1984

Dietary modification of fatty acid and prostaglandin synthesis in the rat. Effect of variations in the level of dietary fat.

Dietary supplements with safflower oil, linseed oil, cod liver oil and hydrogenated coconut oil were given to rats at levels of 5, 20 and 40 energy % to simultaneously assess the effects of both type and level of dietary fat on tissue fatty acid composition and prostanoid synthesis. There was no significant change in weight gain or blood pressure between the dietary groups after the 4-week dietary regimen. The liver oil and linseed oil diets depressed the arachidonic acid content of kidney phospholipids at all levels of supplementation. The arachidonic acid content of plasma lipids was significantly elevated in animals on the safflower oil diet at 20 and 40 energy % while those on the same level of liver oil diet showed a marked reduction in arachidonic acid. Whole blood synthesis of thromboxane B2 varied significantly at all levels of fat supplementation, with the 20 energy % safflower oil fed group showing maximally enhanced thromboxane B2 production compared to the coconut oil group (P less than 0.001). Conversely, the liver oil groups showed depressed thromboxane B2 synthesis at 20 and 40 energy % (P less than 0.01) compared to the coconut oil group and at 5 energy % compared to the safflower oil group (P less than 0.05). Production of 6-ketoprostaglandin F1 alpha and prostaglandin E2 by incubated kidney homogenates only differed significantly between the dietary groups at 40 energy %. Urinary excretion of 6-ketoprostaglandin F1 alpha was increased by 45% and 55% in rats fed the safflower oil diet at 20 and 40 energy %, respectively compared to the saturated fat diet, while in the liver oil groups excretion was reduced by 20% and 32%. Dietary suppression of prostanoid synthesis is explained in part by changes in available arachidonic acid and competitive inhibition of cyclooxygenase by (n - 3) fatty acids. Thus, minor changes in dietary fat can readily alter tissue fatty acid composition, but both the extent and nature of changes in phospholipid and prostanoid metabolism vary markedly according to the tissue site.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Dietary-induced changes in the fatty acid composition of human cheek cell phospholipids: correlation with changes in the dietary polyunsaturated/saturated fat ratio.

Healthy normotensive volunteers aged 20 to 59 yr were randomly allocated either to a control group or to one of two experimental groups. The control group ate a low P/S ratio diet for 12 wk while the first experimental group ate a high P/S ratio diet for 6 wk followed by a low P/S ratio diet for the next 6 wk. The second experimental group ate a low P/S ratio diet in the first 6 wk followed by a high P/S ratio diet for the next 6 wk. Dietary P/S ratio, plasma linoleic acid (18:2), and cheek cell phospholipid 18:2 levels were compared in each dietary group at the end of the 1st and 2nd 6 wk. On change from a low to a high P/S ratio diet, there was a 36% increase in the proportion of 18:2 in the cheek cell phospholipids in comparison with the proportion existing before the change. This was associated with an increase in the proportion of 18:2 in the plasma lipids of this group. No reduction in the proportion of 18:2 in the cheek cell phospholipids was apparent in the control group or the group which changed from a high to a low P/S ratio diet, although in the latter group there was a reduction in the proportion of 18:2 in the plasma lipids. As the phospholipid fatty acid composition of human cheek cells reflects dietary lipid status under certain conditions, this observation may be useful in dietary and nutritional studies, particularly as human cheek cells can be obtained in a noninvasive manner.

Adult↗