Effects of dietary oleic, linoleic and alpha-linolenic acids on blood pressure, serum lipids, lipoproteins and the formation of eicosanoid precursors in patients with mild essential hypertension.

Forty-four male in-patients with mild essential hypertension were randomly allocated to three groups and put on diets supplemented with 60 ml/day of olive (n = 15), sunflowerseed (n = 15) or linseed oils (n = 14), respectively, for two weeks within a blind study. In the group receiving sunflowerseed oil an increase of linoleic acid in serum lipids could be observed, whereas arachidonic and eicosapentaenoic acids appeared unchanged in serum triglycerides and even significantly lower in cholesterol esters. The subjects ingesting the linseed oil-rich diet showed an increase of alpha-linolenic acid in serum lipids, whereas arachidonic and eicosapentaenoic acids remained unchanged in serum triglycerides. In cholesterol esters, however, arachidonic acid was significantly decreased and eicosapentaenoic acid appeared increased only to a low level of significance. In the group put on the olive oil-rich regimen only a significant fall of linoleic acid was obvious in serum triglycerides. The results might indicate a defective desaturation and elongation of linoleic and alpha-linolenic acids and, consequently, a slow formation of arachidonic and eicosapentaenoic acids in patients with mild essential hypertension, which should be considered in dietary studies. After the sunflowerseed oil-rich diet a significant decrease of total cholesterol, low density lipoprotein (LDL) cholesterol and the LDL/high density lipoprotein (HDL) cholesterol ratio was found. Systolic blood pressure during a psychophysiological stress test and urinary sodium excretion appeared significantly lower after the linoleic acid-rich diet. After the linseed oil-rich diet, in addition to total cholesterol, LDL cholesterol and the LDL/HDL cholesterol ratio, serum triglycerides and lecithin cholesterol acyl transferase (LCAT) activity were significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Action of cholestane-3 beta,5 alpha,6 beta-triol on rats with particular reference to the aorta.

Cholestane-3 beta,5 alpha,6 beta-triol, administered orally to rats in different doses and for varying lengths of times, effected toxic cell damage on aortic smooth muscle cells and endothelium. Cholesterol, applied in the same doses, did not lead to appreciable alterations of the aorta. After parenteral application of lipids with simultaneous administration of cholestane-triol there were no demonstrable fat deposits in the damaged aortic wall with angiotensin II (AII) induced hypertension. Thus, there was no recognizable influence of hypertension on increased fat passage in the arterial wall, or any action of lipids to enhance the permeability of vessels. However, the hypertension had an exacerbating effect in so far as in animals with AII-induced blood pressure rise alterations of the media were more pronounced after cholestane-triol, although we were unable to rule out a primary effect of AII. A potentiation of the cholestane-triol action by simultaneous application of cholesterol demonstrated for the rabbit did not occur in rats. Blood content was lowered mostly by cholestane-triol, also by cholesterol. HDL-cholesterol was little affected; almost no influence was observed in triglycerides. The strong cytotoxic action of cholestane-triol underlines its health-damaging role. Due to its action on the aorta of the rat, despite the animal's resistance to arteriosclerosis, involvement of this cholesterol derivative in the pathogenesis of arteriosclerotic alterations can not be excluded.

Long-term effect of mackerel diet on blood pressure, serum lipids and thromboxane formation in patients with mild essential hypertension.

Twelve male patients with mild essential hypertension were put on a diet supplemented with 2 cans of mackerel/day (= 2.2 g daily of eicosapentaenoic acid, EPA, C20:5 n-3 and 2.8 g daily of docosahexaenoic acid, DHA, C22:6 n-3) for 2 weeks within an isocaloric regimen and then with 3 cans/week (= 3.3 g/week, equivalent to 0.47 g daily of EPA and 4.2 g/week, equivalent to 0.69 g daily of DHA) for 8 months with a subsequent period of 2 months on normal diet. Eleven male hypertensives matched for age, body weight index, blood pressure and serum lipids with no change in their nutritional habits served as controls. After the first dietary period (2 weeks) a significant decrease of serum triglycerides (TG), total and LDL-cholesterol, blood pressure and thromboxane B2 (TxB2) was found, whereas HDL cholesterol and potassium in erythrocytes were significantly increased. During the second dietary period (8 months) providing the lower dose of EPA, serum lipids and the other biochemical parameters returned to the initial values. Blood pressure, however, remained significantly lower and rose to the basal levels only after the third period (2 months) on normal diet. In the control group no alterations could be seen. The data suggest a dose-related differential effect of dietary EPA on serum lipids, lipoproteins, TxB2 and blood pressure in subjects with mild hypertension.

Slow desaturation and elongation of linoleic and alpha-linolenic acids as a rationale of eicosapentaenoic acid-rich diet to lower blood pressure and serum lipids in normal, hypertensive and hyperlipemic subjects.

In normal, hypertensive and hyperlipemic subjects, diets supplemented with linoleic acid (LA) or alpha-linolenic acid (LNA) resulted in an increase of the corresponding fatty acids in serum lipids. However, their C20-derivatives, the prostaglandin precursors arachidonic acid (AA) and eicosapentaenoic acid (EPA), respectively, were not or only slightly augmented. On the other hand, an EPA-rich diet produced a marked increase of this fatty acid, especially in cholesterol esters. After this diet the decreases of blood pressure and serum lipids were more pronounced when compared with LA- and LNA-rich diets containing a 20-fold higher dose of the polyunsaturated fatty acids. The slow formation of AA and EPA from LA and LNA seems to be a characteristic finding in humans, being different from preferred laboratory animals, for instance, rats. This observation was independent of the presence of risk factors, like arterial hypertension or hyperlipoproteinemia (HLP).

Serum triglycerides and HDL cholesterol from SHR after evening primrose oil and other polyunsaturated fats.

Spontaneously hypertensive rats (SHR) were fed diets enriched with evening primrose (EPO), sunflower (SO) and linseed oils (LO) as well as palm kernel fat (PKF), the latter being deficient in polyunsarated fatty acids (PUFA). In SHR fed EPO serum triglycerides were lowest and HDL1 cholesterol was highest as compared to the other groups of animals. Total cholesterol was not different. The data suggest that - as with blood pressure - serum lipids and lipoproteins might be influenced most effectively by EPO in comparison to other polyunsaturated fats.

[Changes in blood pressure and serum lipids with fish diets in patients with mild essential hypertension]. / Anderungen von Blutdruck und Serumlipiden unter Fischdiäten bei Patienten mit milder essentieller Hypertonie.

14 male patients with moderate essential hypertension were treated in the cross-comparison with a mackerel and herring diet, respectively, for two weeks. The mackerel diet contained double as much eicosapentaenic (EPA) and docosahexaenic acid (DHA) as the herring diet which served as control. In the serum triglycerides particularly DHS, in the cholesterol esters above all EPA were enriched. In the phospholipids the increase of the two fatty acids was approximately the same. At the end of the mackerel period the serum triglycerides, the total and LDL-cholesterol, the activity of the lecithin-cholesterol-acyl-transferase (CALT) and the serum sodium were significantly decreased. On the other hand, the HDL-cholesterol and the uric acid in the serum significantly increased. Under influence of the herring diet the parameters mentioned appeared only slightly changed. After the mackerel diet also a significantly lower systolic blood pressure was found. The systolic and diastolic blood pressure during a standardized psychophysiological stress test was more diminished at the end of the mackerel period than after the herring diet. The plasma renin activity (PRA) was increased after the mackerel diet. Its increase under the stress test could no more be proved at the end of the mackerel diet. In similar way the stress-conditioned increase of thromboxane B2 could no more be observe both after mackerel and after herring diet. When the results should confirm themselves in long-term studies, a mackerel diet in practicable dosage can be recommended as non-medicamentous treatment of moderate hypertension.

Blood pressure- and lipid-lowering effect of mackerel and herring diet in patients with mild essential hypertension.

Fourteen male patients with mild essential hypertension were put on a mackerel and herring diet within a prescribed isocaloric regimen in a cross-over design for 2 weeks. After mackerel diet eicosapentaenoic acid (EPA-C20:5, n-3) appeared more in cholesterol esters (1.7-11.0%), whereas docosahexaenoic acid (DHA-C22:6, n-3) was predominantly incorporated into serum triglycerides (1.0-8.3%). After herring diet, which contained half as much EPA and DHA, their increase was of minor degree. After mackerel diet serum triglycerides, total cholesterol, LDL cholesterol and lecithin cholesterol acyl transferase (LCAT) activity were significantly decreased (by 28%, 9%, 14% and 14%, respectively), returning to the initial levels 3 months later. On the contrary, HDL cholesterol appeared significantly increased (by 12%). After herring diet the differences were not significant. Serum sodium was significantly lower (by 2%) at the end of the mackerel diet as compared to the initial values. On the other hand, uric acid in serum appeared transiently increased (by 24%) at the end of both dietary periods. A significant decrease (by 8%) in casual systolic blood pressure, measured in recumbent position, could be observed only at the end of the mackerel period. Moreover, the level of systolic and diastolic blood pressure before and during a standardized psychophysiological stress test was significantly lower after mackerel diet. Nevertheless, the increments after stress were similar. Plasma renin activity was increased (by 64%) after mackerel diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence on serum lipids, lipoproteins and blood pressure of mackerel and herring diet in patients with type IV and V hyperlipoproteinemia.

Eight patients with type IV and V hyperlipoproteinemia were put on a mackerel and herring diet of an isocaloric regimen for 2 weeks, in a cross-over design. At the end of the dietary periods a predominant increase of eicosapentaenoic acid (EPA - C20:5, n-3) in cholesterol esters and of docosahexaenoic acid (DHA - C22:6, n-3) in serum triglycerides, being more pronounced after mackerel as compared to herring diet, could be confirmed. After mackerel diet serum triglycerides and total cholesterol were significantly lower, returning to basal levels 3 months later. High density lipoprotein (HDL) cholesterol appeared slightly increased after mackerel diet and decreased to initial values thereafter. After herring diet, which contained half as much EPA as compared to mackerel diet, the differences were minor. The decline of free fatty acids (FFA) and insulin at the end of the mackerel period reached the level of significance 60 min and 120 min, respectively, after glucose load. A significantly lower systolic blood pressure in recumbent and upright position after the mackerel period could be found, whereas diastolic pressure and blood pressure after herring diet remained unchanged.

Blood pressure lowering effect of eicosapentaenoic acid-rich diet in normotensive, hypertensive and hyperlipemic subjects.

A mackerel diet or a herring diet in which two cans of fish fillet were consumed daily over 2 weeks within a prescribed regimen, in a crossover design, were given to 15 normotensive volunteers, 14 patients with mild essential hypertension and eight patients with type IV and V hyperlipoproteinemia (HLP). In normotensives a markedly lower systolic and diastolic blood pressure at the end of the period on the mackerel diet could be observed, whereas in hypertensive and hyperlipemic subjects only systolic blood pressure was significantly decreased. After the herring diet, which served as control, changes in blood pressure were of a minor degree.

Postprandial hyperinsulinemia in patients with mild essential hypertension.

Glucose tolerance tests and diurnal profiles of glucose, insulin, free fatty acids, serum triglycerides, total and high-density lipoprotein cholesterol levels were performed in 8 male patients with mild essential hypertension as well as in 20 normotensive subjects. Although glucose tolerance and postprandial glucose levels appeared equal in both groups, the insulin response after a glucose load and after each meal was significantly increased in hypertensive subjects as compared with the controls (p less than 0.01). The levels of free fatty acids were higher in the postabsorptive phase of patients with hypertension in comparison to normotensive subjects, but decreased markedly when plasma insulin levels rose after meals. In both subject groups serum triglyceride levels showed the typical postprandial increase. Total and high-density lipoprotein cholesterol levels showed neither diurnal variations nor differences between hypertensive subjects and normotensive controls. Postprandial hyperinsulinemia in patients with mild essential hypertension possibly may provoke lipid accumulation in the arterial wall and therefore may be a relevant risk factor for atherosclerosis in these subjects.

Changes of arachidonic acid in phosphatidylcholine different from other lipids in kidneys of spontaneously hypertensive rats after feeding a linoleic acid-rich diet.

In spontaneously hypertensive rats (SHR) fed a linoleic acid-rich (LAR) diet over 22 weeks blood pressure could not be influenced when compared with SHR on linoleic acid-deficient (LAD) food. On the other hand, normotensive Wistar rats (WR) revealed a significantly lower blood pressure after feeding a LAR diet. The percentages of LA and AA were markedly increased in triglycerides and free fatty acids (FFA) in renal cortex and medulla of LAR-fed SHR and WR in comparison to LAD-fed animals. In renal phosphatidylethanolamine (PE) LA was also increased whereas AA remained unchanged. On the contrary, in phosphatidylcholine (PC) LA was only slightly augmented (in SHR) or even lowered (in WR), AA appearing decreased in SHR but increased in WR. These different changes in PE and PC indicate that individual phospholipids show a dissimilar behavior after dietary interventions, which can be masked by the evaluation of total phospholipids and might be of pathophysiological relevance.

Age-dependent alterations of linoleic, arachidonic and eicosapentaenoic acids in renal cortex and medulla of spontaneously hypertensive rats.

The lipid content as well as the fatty acid pattern of triglycerides, free fatty acids (FFA), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were estimated in renal cortex and medulla of spontaneously hypertensive rats (SHR) and normotensive Wistar rats (WR) at 4, 8, 26 and 52 weeks of age. In general, the level of triglycerides in renal medulla appeared higher when compared with the cortex. On the other hand, PC and PE, increasing with age, were usually higher in the cortex. A decreased percentage of linoleic acid (LA) in triglycerides, of arachidonic acid (AA) in PC and of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE could be found in the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension. This was accompanied with a rise of AA in FFA of SHR at 8 weeks of age, which occurred with delay in WR (at 26 weeks of age). From the data presented it can be concluded that systematic alterations in the availability of individual polyunsaturated fatty acids (PUFA) in various renal lipids might be related to the onset of hypertension in SHR which should be elucidated in more detail.

Mono-, di- and triglycerides in serum of spontaneously hypertensive and normotensive rats in relation to age.

Serum triglycerides appeared significantly lower in spontaneously hypertensive as compared to normotensive rats except in 8-week-old animals. Tri-, di and monoglycerides decreased continuously with age in the former but revealed only a transient fall in the latter. The remarkably high portion of partial glycerides (about 30% of total glycerides) in serum should be considered in all studies on lipolysis in rats.

Decrease of arachidonic acid in phosphatidylcholine from renal medulla of SHR after feeding a linoleic and linolenic acid-rich diet.

Linoleic acid-rich (LAR), linolenic acid-rich (LNAR) and linoleic acid-deficient (LAD) diets in spontaneously hypertensive rats (SHR) and normotensive rats (NR) resulted in various changes in n-6 and n-3 fatty acids of lipids in renal medulla. After LAR diets the percentage of linoleic (LA) and arachidonic acids (AA) was high only in triglycerides (TG) and free fatty acids (FFA). In phosphatidylethanolamine (PE) LA was increased after LAR diet, whereas AA remained unchanged. In phosphatidylcholine (PC) LA was higher, but AA appeared lower as compared to LAD fed SHR. After LNAR diet linolenic (LNA) and eicosapentaenoic acids (EPA) were increased, but AA appeared significantly lower. Consequently, the lowest percentage of AA was found after LNAR diet. Blood pressure could not be influenced by the diets.

Alterations of linoleic, arachidonic and eicosapentaenoic acids in renal cortex and medulla of SHR during the onset of hypertension.

104 spontaneously hypertensive rats (SHR) and 107 normotensive control rats (WR) fed a commercial diet were sacrificed at 4, 8, 26 and 52 weeks of age. The kidneys were immediately removed and carefully separated into cortex and medulla. In general, the triglyceride levels in renal medulla appeared higher when compared with the cortex. On the other hand, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were usually higher in the cortex and increased with age. In the kidneys of SHR at 8 weeks of age, i.e. during the development of hypertension, the percentage of linoleic acid (LA) in triglycerides and of arachidonic acid (AA) in PC was decreased. This was associated with an increase of AA in free fatty acids (FFA), indicating an enhanced activity of phospholipase A2. Furthermore, a fall of eicosapentaenoic acid (EPA) in triglycerides, FFA, PC and PE of kidneys in SHR at 8 weeks of age could be found. The data suggest that systematic alterations in the availability of individual polyunsaturated fatty acids in various renal lipids might be related to the onset of hypertension in SHR. Age-dependent changes in enzymes involved in prostaglandin formation should be considered as an adaptive mechanism which is insufficient to reduce or abolish genetically determined hypertension in SHR.

Clinical studies on lipid and blood pressure lowering effect of eicosa-pentaenoic acid-rich diet.

15 volunteers were put on a mackerel (MD) and herring diet (HD) for 2 weeks in a cross-over design. At the end of the dietary periods eicosa-pentaenoic acid (EPA) was predominantly incorporated into cholesterol esters (CE), whereas docosahexaenoic acid (DHA) appeared more in triglycerides (TG). This was more pronounced after MD as compared to HD. After MD a significant decrease of serum TG, total cholesterol (C) and lecithin cholesterol acyl transferase (LCAT) activity could be observed returning to the initial levels 3 months later. After HD only a decrease of LCAT was significant. In addition, a marked decrease in blood pressure (BP) was associated with lower plasma noradrenaline levels after MD, but not after HD. In 14 patients with mild essential hypertension an enhanced percentage of EPA and DHA in the lipids of VLDL, LDL and HDL could be confirmed. After MD serum TG, C, LDL-C and LCAT were significantly decreased, whereas HDL-C appeared increased. After HD the changes were of minor degree. Systolic BP was significantly lower at the end of MD. In 8 patients with type IV and V hyperlipoproteinemia (HLP) similar changes could be seen, the most striking finding being a fall in serum TG, especially if initial values were extraordinarily high. The data suggest a beneficial effect of MD on several parameters known as risk factors of atherosclerosis.