Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Dietary fish oils reduce plasma levels of platelet activating factor precursor (lyso-PAF) in rats. 370 10

The effect of dietary fish oils on development of hypertension and vascular response in vitro were studied in rats and a primate. Dietary fish oils (MaxEPA and an n-3 ethyl ester concentrate of higher EPA and DHA content) were administered to spontaneously hypertensive (SHR), stroke-prone spontaneously hypertensive (SHR-SP) and a backcross of SHR and Wistar Kyoto (SHR/WKY) rats from 4-16 weeks of age. Blood pressure was monitored during the feeding period and vascular responses measured in the aorta and mesenteric vascular bed in vitro. Depending on the strain of rat used and the composition of the fish oil the attenuation in blood pressure was 10-26 mmHg. Fish oils attenuated the response mediated by sympathetic nerve stimulation or intralumenal norepinephrine in the perfused mesenteric vascular bed preparation from the SHR. This attenuation was more pronounced for fish oils enriched with eicosapentaenoic acid and docosahexaenoic acid and was more prominent in the SHR and SHR/WKY backcross than it was in the SHR-SP. Prostanoid synthesis or nitric oxide modulation of alpha-adrenoceptor responses were shown not to be involved in the attenuation of vascular responses produced by fish oil. The maximum contraction of aortic ring preparations in response to norepinephrine (NE) was significantly smaller in SHR than WKY rats fed olive oil and for SHR rats maintained on fish oils the contraction was close to WKY olive oil values. Evidence was obtained also for a modulation of vasoconstrictor responses by dietary fish oils in the perfused mesenteric bed of the marmoset monkey.
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PMID:Fish oils modulate blood pressure and vascular contractility in the rat and vascular contractility in the primate. 767 Jun 52

Increased vascular collagen content is a major feature of pulmonary vascular remodeling. The functional role of excess collagen in decreasing pulmonary vascular compliance has not been established. We determined whether there was a correlation between hydroxyproline content of rat pulmonary artery segments and elastance (EPA) of the pulmonary artery bed during development of hypoxic pulmonary hypertension (10% O2, 10 d) and normoxic recovery. EPA was measured by air-filled pressure-volume curves. After 10 d of hypoxia, hydroxyproline content increased approximately 2-fold in large segments (1,200-250 microns in diameter) but not significantly in small segments (> 250 microns). Elastance increased from 87 +/- 6 (SEM) to 145 +/- 8 mm Hg/ml (p < 0.05) within 5 d of hypoxia and returned to control value 3 wk after recovery. There was a correlation between collagen content and EPA in large segments during development of hypertension; no correlation was found during recovery from hypoxia. The ratio of hydroxyproline to total protein was unchanged in large segments after recovery from hypoxia but was increased in small segments after recovery. We conclude that increased collagen in large pulmonary arteries directly influences EPA during the development of hypoxic pulmonary hypertension.
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PMID:Excess collagen in hypertensive pulmonary arteries decreases vascular distensibility. 817 73

Dietary fish oils rich in n-3 polyunsaturated fatty acids can modulate a diverse range of factors contributing to cardiovascular disease. This study examined the relative roles of eicosapentaenoic acid (20:5 n-3; EPA) and docosahexaenoic acid (22:6 n-3; DHA) which are the principal n-3 polyunsaturated fatty acids regarded as candidates for cardioprotective actions. At low dietary intakes (0.4-1.1% of energy (%en)), docosahexaenoic acid but not eicosapentaenoic acid inhibited ischaemia-induced cardiac arrhythmias. At intakes of 3.9-10.0%en, docosahexaenoic acid was more effective than eicosapentaenoic acid at retarding hypertension development in spontaneously hypertensive rats (SHR) and inhibiting thromboxane-like vasoconstrictor responses in aortas from SHR. In stroke-prone SHR with established hypertension, docosahexaenoic acid (3.9-10.0%en) retarded the development of salt-loading induced proteinuria but eicosapentaenoic acid alone was ineffective. The results demonstrate that purified n-3 polyunsaturated fatty acids mimic the cardiovascular actions of fish oils and imply that docosahexaenoic acid may be the principal active component conferring cardiovascular protection.
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PMID:The cardiovascular protective role of docosahexaenoic acid. 874 Nov 70

The purpose of the present study was to investigate the effect of a concentrated preparation (EPA 30) containing eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3) on the limiting desaturation steps of the polyunsaturated fatty acid biosynthesis in spontaneously hypertensive rats (SHR). Adult SHR were divided into two groups: one group received a standard diet, and the experimental group the standard diet including 0.8% of EPA30 for 9 weeks. Blood pressure was measured at the end of the diets. The desaturase activities and fatty acid composition were determined in isolated hepatocytes. The blood pressure did not decrease in the experimental group. The desaturated products of the n-6 family (gamma-linolenic acid, 18:3 n-6 and arachidonic acid, 20:4 n-6) were lowered in the EPA30 group, when their respective substrates (18:2 n-6 and 20:3 n-6) were increased. EPA and DHA were higher in the experimental group delta 6 n-3, delta 6 n-6 and delta 5 n-6 desaturase activities were depressed approximately 20% in the EPA30 group. EPA30 being an active nutrient on the EFAs cascade, increasing the level of PG3 precursors and decreasing the level of PG2 precursors, favourable conditions have been established to reduce hypertension. The underlying mechanism related to the regulation of desaturase activities by these fatty nutrients remains to be elucidated.
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PMID:Fatty acid metabolism, pharmacological nutrients and hypertension. 920 10

The objective of this study was to determine the effect of ethyl eicosopentate (EPA-E) on local cerebral blood flow (1-CBF) and local glucose utilization (1-CGU) in specific regions of the brain in stroke-prone spontaneously hypertensive rats (SHRSP). EPA-E (100 mg/kg body weight) or saline was orally administered to 8-week-old SHRSP. L-CBF and 1-CGU in the EPA-E-treated, saline-treated, and 8-week-old control rats were measured autoradiographically using 14C-iodoantipyrine and 14C-deoxyglucose (Sakurada's and Sokoloff's methods). The 1-CBF of the saline-treated group decreased significantly with age in all areas measured. EPA-E treatment alleviated the age-dependent decrease in 1-CBF in all areas, especially those in the basal ganglia. The 1-CGU of the saline-treated group did not change with age, however EPA-E treatment increased 1-CGU in all areas measured, though the changes were not significant. EPA-E ameliorated the decrease in cerebral blood flow and improved glucose metabolism in SHRSP suffering from severe hypertension. These results suggest that EPA-E may be useful in the prevention of stroke.
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PMID:Effect of long-term administration of ethyl eicosapentate (EPA-E) on local cerebral blood flow and glucose utilization in stroke-prone spontaneously hypertensive rats (SHRSP). 925 29

Highly concentrated marine polyunsaturated fatty acids (n-3 PUFA), affecting the lipids and lipophilic drugs metabolism, can interfere with cyclosporine (CyA) pharmacokinetics. This prospective, randomized and placebo-controlled, double-blind study involved 42 kidney graft recipients. From day +1, 21 pts (E) received 6 g n-3 PUFA (85% EPA + DHA, Esapent, Pharmacia) and 21 pts (P) received placebo (olive oil), both reduced to 3 g from day +30 on. A quadruple immunosuppressive regimen was employed. Plasma creatinine, lipids and CyA pharmacokinetics were investigated 1, 3, 6, 9 and 12 months after graft. The two groups were comparable for age, weight, M/F ratio, hypertension prevalence and baseline lipids. Active treatment did not affect total and HDL-cholesterol, but significantly lowered triglycerides (E:120 +/- 12 vs P:166 +/- 21 mg/dl, p < 0.0001). At one year, E pts had lower creatinine than P (1.26 +/- 0.06 vs. 1.88 +/- 0.2 mg/dl, p < 0.05), comparable CyA dosage, and a larger CyA area under the curve (AUC) (n.s.), with a higher blood peak level (Cmax) (p < 0.04) and less variance in time to peak (n.s.). The larger AUC in the E group at all intervals and the better pattern of plasma creatinine, with no rise in blood pressure, provided evidence of better CyA absorption and metabolism in n-3 PUFA supplemented kidney graft recipients.
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PMID:Effect of n-3 polyunsaturated fatty acids on cyclosporine pharmacokinetics in kidney graft recipients: a randomized placebo-controlled study. 958 80

Cod liver oil (CLO) is known to contain a complex mixture of triacylglycerols (TAGs) in which the component fatty acids include: myristic (C(14:0), M), C(14:1) (M(1)), palmitic (C(16:0), P), palmitoleic (C(16:1), P(1)), stearic (C(18:0), S), oleic (C(18:1), O), linoleic (C(18:2), L), arachidic (C(20:0), A), C(20:1) (A(1)), eicosapentaenoic (EPA, C(20:5), A(5)), docosanoic (C(22:0), D), docosaenoic (C(22:1), D(1)), and docosahexaenoic (DHA, C(22:6), D(6)). Because of the presence of EPA and DHA in cod liver oil, it has been used for several generations as a nutritional supplement, and recommended for the relief of various physiological ailments including arthritis, depression, and high blood pressure. Consequently, it was of interest to develop a sample preparation protocol that would enable rapid screening of such a chemically complex and nutritionally useful oil. Thus, we have analyzed two commercial brands of cod liver oil by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS). There was no significant difference between the mass spectral profile of the two CLO brands. alpha-Cyano-4-hydroxycinnamic acid, dissolved in acetonitrile/tetrahydrofuran, was used as the matrix. MALDI-TOFMS produced only sodiated triacylyglycerol molecules [M + Na](+). Based on the sodiated TAGs, 64 TAG assignments were made, and these include MM(1)L, MML, MMO and MMS, M(1)P(1)L MP(1)L, P(1)P(1)P, PPP, P(1)P(1)Ln, P(1)PLn, PPL, PPO, P(1)LnLn, PLnLN, PLLn, PLL, POL, POO, P(1)A(6)Ln, P(1)A(5)Ln, P(1)A(5)L, PA(5)L PA(5)O, PP(1)D(6), OOL, OOO, SOO, SSS, P(1)LnD(6), PLnD(6), PLD(6), POD(6) (or P(1)A(5)A(1)), PA(5)A(1), OLA, OLA(1), SLA(1), SOA(1), SSA, LA(5)A(5) (or P(1)A(5)D(6)), OA(5)A(5) (or PA(5)D(6)), SA(5)A(5), LnA(1)A(5), OOD(6), SOD(6), SSD(6), LA(1)D(6), OA(1)D(6), OA(5)D(6), SA(5)D(6), SA(5)D(5), D(6)A(1)O, D(6)A(1)S, D(1)A(1)O, DA(1)O, D(1)D(6)O, and DD(6)O. The sample preparation method developed in this study could be used for the routine screening of oils that contain similar types of polyunsaturated TAGs.
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PMID:Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of cod liver oil and the effect of analyte/matrix concentration on signal intensities. 1045 46

Docosahexaenoic acid (DHA) is essential for the growth and functional development of the brain in infants. DHA is also required for maintenance of normal brain function in adults. The inclusion of plentiful DHA in the diet improves learning ability, whereas deficiencies of DHA are associated with deficits in learning. DHA is taken up by the brain in preference to other fatty acids. The turnover of DHA in the brain is very fast, more so than is generally realized. The visual acuity of healthy, full-term, formula-fed infants is increased when their formula includes DHA. During the last 50 years, many infants have been fed formula diets lacking DHA and other omega-3 fatty acids. DHA deficiencies are associated with foetal alcohol syndrome, attention deficit hyperactivity disorder, cystic fibrosis, phenylketonuria, unipolar depression, aggressive hostility, and adrenoleukodystrophy. Decreases in DHA in the brain are associated with cognitive decline during aging and with onset of sporadic Alzheimer disease. The leading cause of death in western nations is cardiovascular disease. Epidemiological studies have shown a strong correlation between fish consumption and reduction in sudden death from myocardial infarction. The reduction is approximately 50% with 200 mg day(-1)of DHA from fish. DHA is the active component in fish. Not only does fish oil reduce triglycerides in the blood and decrease thrombosis, but it also prevents cardiac arrhythmias. The association of DHA deficiency with depression is the reason for the robust positive correlation between depression and myocardial infarction. Patients with cardiovascular disease or Type II diabetes are often advised to adopt a low-fat diet with a high proportion of carbohydrate. A study with women shows that this type of diet increases plasma triglycerides and the severity of Type II diabetes and coronary heart disease. DHA is present in fatty fish (salmon, tuna, mackerel) and mother's milk. DHA is present at low levels in meat and eggs, but is not usually present in infant formulas. EPA, another long-chain n-3 fatty acid, is also present in fatty fish. The shorter chain n-3 fatty acid, alpha-linolenic acid, is not converted very well to DHA in man. These longchain n-3 fatty acids (also known as omega-3 fatty acids) are now becoming available in some foods, especially infant formula and eggs in Europe and Japan. Fish oil decreases the proliferation of tumour cells, whereas arachidonic acid, a longchain n-6 fatty acid, increases their proliferation. These opposite effects are also seen with inflammation, particularly with rheumatoid arthritis, and with asthma. DHA has a positive effect on diseases such as hypertension, arthritis, atherosclerosis, depression, adult-onset diabetes mellitus, myocardial infarction, thrombosis, and some cancers.
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PMID:Health benefits of docosahexaenoic acid (DHA) 1047 62

We investigated the effect of long-term administration of highly purified eicosapentaenoic acid ethyl ester (EPA-E), an n-3 polyunsaturated fatty acid derived from fish oil, in comparison to lard on the development of hypertension and insulin resistance in Dahl salt-sensitive (Dahl-S) rats fed a high-sucrose diet (HSD), a model of salt-sensitive hypertension. After 16 weeks of treatment, the glucose infusion rate (GIR) during the euglycemic insulin-glucose clamp test significantly increased in the HSD-EPA-E group compared with the HSD-water or -lard control group. The GIR was approximately three times higher in the HSD-EPA-E group versus the HSD-water or -lard control group, and it was about 70% of the rate in the calorically deprived control group fed a low-fat-high-fiber diet (LF-HFD). In addition, EPA-E significantly suppressed the elevation of plasma glucose and insulin levels after oral glucose loading. These results indicate that EPA-E prevents the development of insulin resistance in Dahl-S rats fed a HSD. Fatty acid analysis of phospholipids in skeletal muscle showed a significant increase in C18:2, C20:5, and C22:5 components in the HSD-EPA-E group and, conversely, a significant decrease in C16:0, C20:4, and C22:6. The present results indicate that the beneficial effect of EPA-E on insulin resistance in Dahl-S rats fed a HSD is likely dependent on the modification of phospholipid components in the skeletal muscle membrane. These findings suggest that EPA-E might prevent the development of insulin resistance in dietary obesity. In addition, the HSD-EPA-E group showed a significant increase in the level of uncoupling protein (UCP) in brown adipose tissue as compared with the HSD-water or -lard control group. However, EPA-E had no effect on the development of hypertension and obesity in Dahl-S rats fed the HSD.
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PMID:Effect of highly purified eicosapentaenoic acid ethyl ester on insulin resistance and hypertension in Dahl salt-sensitive rats. 1048 46


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