A long-term fish diet modifies the toxic properties of human partially oxidized LDL on vascular preparations in vitro.

Both LDL oxidation and LDL fatty acid composition affect vascular relaxation and contraction. The aim of this study was to investigate whether long-lasting dietary habits (vegetarian, fish and high saturated fat as a control group) can change those properties of partially oxidized LDL (ox-LDL) which are reflected in altered vascular responses measured with a bioassay. The effects of ox-LDL were investigated on rat mesenteric arteries. In endothelium intact arterial rings the contractile responses to noradrenaline (NA) tended to be diminished in the presence of ox-LDL derived from the fish diet group compared with the other groups. In the endothelium denuded arterial rings the contractile responses to NA and KCl were significantly enhanced by ox-LDL from the fish diet group compared with the control group. The ox-LDL from the fish diet group increased the diclofenac, L-NAME resistant relaxations to ACh compared to the control diet group suggesting the role of endothelium derived hyperpolarizing factor (EDHF). In conclusion, partially oxidized LDL from subjects living on a fish diet is biologically more vasoactive in bioassay systems than partially oxidized LDL from those living on vegetarian or saturated fatty acid containing diets. The impaired responses in vasoconstriction and improved vasodilation seem to be endothelium dependent.

Dietary habits affect the susceptibility of low-density lipoprotein to oxidation.

OBJECTIVE: To study, if there are differences in the fatty acid composition of low-density lipoprotein (LDL) in people eating three different long-standing habitual diets: vegetarian, high fish intake, or high saturated fat (milk fat) diet as a control group, and to study if these differences influence the oxidation susceptibility of LDL. DESIGN: Cross-sectional study using blood samples and a validated dietary frequency questionnaire with illustrations. SETTING: Helsinki University Central Hospital, Finland. SUBJECTS: The effect of three different types of long-standing diets of different fatty acid content (a strict vegetarian diet, n=11; a high fish intake diet, n=9; and a high saturated fat (milk fat) diet, controls, n=7) on the serum and LDL fatty acid content, and on the susceptibility of LDL to oxidation in vitro, was studied in healthy normocholesterolemic volunteers who had been on these diets for years. Oxidation of LDL was carried out by using CuSO4 as a pro-oxidant. RESULTS: There were no statistically significant differences in the serum lipids or lipoproteins, though the vegetarian group exhibited lowest mean values of total, high-density lipoprotein (HDL) and LDL cholesterol levels. Both the serum and LDL eicosapentaenoic, docosapentaenoic and docosahexaenoic acid proportions were highest in the fish and lowest in the vegetarian groups. Linoleic acid was highest among the vegetarians. In the fish group, the vitamin A concentration in serum was higher than in vegetarians and controls and beta-carotene lower than in controls, but in alpha-tocopherol, or lycopene concentrations there were no statistically significant differences. The lag phase of LDL oxidation was shortest (116 min) in the fish group and longest (165 min) in the vegetarian group, and the control group was between them (129 min). The mean oxidation percentage after 2.5 h of copper-induced oxidation was highest (44%) in the fish group and lowest (22%) in the vegetarian group and intermediate (31%) in the control group. CONCLUSION: Long-term dietary habits predict the fatty acid composition of serum and LDL, and influence the susceptibility of LDL to oxidation. In the fish group with the highest content of omega-3 fatty acids in LDL, the oxidation susceptibility of LDL was highest. In the vegetarian group with less omega-3 fatty acids in LDL, the LDL was more resistant to oxidation. SPONSORSHIP: Helsinki University Central Hospital.

Proliferative effects of oxidized low-density lipoprotein on vascular smooth muscle cells: role of dietary habits.

The effects were studied of native, partially-oxidized and totally-oxidized human low-density lipoprotein (LDL) on the proliferation of cultured rat aortic smooth muscle cells (VSMC), measured as an altered DNA synthesis. The LDL was obtained from three different human long-term diet groups (a control diet rich in saturated fats, a vegetarian diet, and a fish diet). The oxidized LDLs were prepared by oxidizing the LDL with copper sulfate. The DNA synthesis was measured by [3H]-thymidine incorporation into the DNA. The partially-oxidized LDL was the most potent promoter of DNA synthesis compared to the native or totally-oxidized LDL of the same diet group. The partially-oxidized LDL had a true mitogenic effect in the absence of exogenous growth factors. The native and totally-oxidized LDL induced a significant increase in DNA synthesis, if they were obtained from the fish diet group. This study suggests an enhanced proliferative effect of partially-oxidized LDL on VSMC growth.

Platelet taurine concentration and uptake in the Brattleboro diabetes insipidus rat.

Since platelets accumulate taurine, they provide a model for studying the taurine transport in anisosmotic disorders. Thus, in this work we studied the taurine concentration and uptake in the platelets of Brattleboro rats, homozygous (DI) and heterozygous (HZ) for hereditary hypothalamic diabetes insipidus, and Long Evans (LE) normal rats after free water intake and after dehydration induced by water deprivation for 24 h. The decreased ability of the DI rats to concentrate urine led to plasma hypernatremia and hyperosmolality despite excessive drinking. Water deprivation in the DI rats induced drastic dehydration with exacerbated hypernatremia and hyperosmolality. Plasma hypernatremia and hyperosmolality resulted in a significant elevation of the taurine concentration and uptake by platelets of the DI rats. Kinetic assays showed that plasma hypernatremia and hyperosmolality did not alter the affinity of taurine to platelet membrane carrier, as expressed by Km, but caused a profound increase in the maximal transport capacity, Vmax. After free water intake the Vmax of the DI rats was about two times higher than that in the HZ and LE rats and after water deprivation it was about three times higher. Water deprivation doubled the Vmax of the DI rats without changing the Km.

Taurine in the osmoregulation of the Brattleboro rat.

The function of taurine in mammalian osmoregulation was studied in the Brattleboro rat with hereditary hypothalamic diabetes insipidus (DI). DI rats are chronically dehydrated because of their inability to synthesize vasopressin. One day of water deprivation did not affect the water balance in rats with normal vasopressin synthesis, whereas DI rats were markedly dehydrated and lost considerably body weight. Taurine content and 3H-taurine accumulation by platelets were significantly higher in DI rats, with a further increase after one day of water deprivation. In DI rats, water deprivation also evoked a clear taurine increase in skeletal muscle and in the brain. These findings indicate that taurine has an osmoregulatory function in mammals.

Taurine in human auricular myocardium and blood platelets.

Blood platelets have been used as a model for the aminergic neurones. In the hypertrophied left ventriles and platelets of spontaneously hypertensive rats the taurine content increases simultaneously. The main purpose of this work was to compare the taurine contents of human platelets and heart tissue. The taurine content was estimated from blood platelets and from the right atrial appendage removed during open heart surgery in 43 patients suffering from ischaemic heart disease. The results indicate that the taurine content increases in the hypertrophied right atrium of the patients with atrial septal defect, as it had previously been shown to increase in the hypertrophied left ventricle in patients who died of congestive heart failure. No correlations were found: 1) between the heart and platelet taurine contents of different groups, 2) between the atrial and platelet taurine in the pooled total results, 3) between the diastolic blood pressure and atrial or platelet taurine levels. Thus the increased taurine content of the auricular tissue is not reflected in the taurine content of the platelets.

beta-Alanine and alpha-L-alanine inhibit the exploratory activity of spontaneously hypertensive rats.

1% beta-alanine and alpha-L-alanine, when given for 7 days as the only drinking fluid, inhibited the exploratory activity of adult male spontaneously-hypertensive rats (SHR) but not that of the normotensive Wistar-Kyoto rats (WKR). beta-Alanine decreased the taurine level in the liver of both strains and in the platelets of SHR. alpha-Alanine decreased the taurine level in the liver of WKR and in the platelets of SHR.

Platelet taurine in patients with arterial hypertension, myocardial failure or infarction.

The content of taurine in the hypertrophied left ventricle is increased in congestive heart failure an in spontaneously hypertensive (SH) rats. In SH rats the taurine content of and taurine uptake by the platelets are also increased. The present results indicate that, as in the heart, the taurine content may also increase in the platelets of those patients with congestive heart failure. The taurine content and uptake are not increased in the platelets of hypertensive patients as they are in the platelets of SH rats. It is likely that in acute myocardial infarction, a considerable amount of taurine is released from the heart into the plasma. However, there is no simultaneous increase in the platelet taurine content. From this work on can only conclude that platelets may reflect taurine changes in the heart in some pathological states, e.g. congestive heart failure.