Yvonne K. Lungershausen

Reduction of blood pressure and plasma triglycerides by omega-3 fatty acids in treated hypertensives.

Objective: To assess the effects of omega-3 (n-3) fatty acid supplementation on blood pressure and plasma lipids in hypertensives treated with diuretics or beta-blockers. Design: Double-blind placebo-controlled cross-over trial consisting of a 4-week run-in phase and two 6-week intervention phases. Patients: A total of 43 patients of either sex taking a beta-blocker only (n = 29), a diuretic only (n = 3) or a beta-blocker plus diuretic (n=11) for hypertension were recruited from general practice. One patient from the latter group was withdrawn. Methods: Seated blood pressure was measured every 2 weeks in the clinic with a Dinamap. After the run-in phase, participants were randomly assigned to take a supplement of either Omacor (85% n-3 fatty acid concentrate) or corn oil (four 1-g capsules/day) for 6 weeks, after which they crossed over to the other supplement. Fasted blood samples were taken at the end of each phase for lipid analysis. Main outcome measures: The within-individual differences in systolic and diastolic pressure and plasma lipids between Omacor and corn oil treatment. Results: Systolic/diastolic blood pressures measured during the run-in phase were normal (132±2/76±1 mmHg, n = 42) but decreased further with n-3 fatty acid supplementation. The mean within-individual difference in blood pressure compared with corn oil supplementation was 3.1 ± 1.0/1.8±0.6 mmHg (P<0.01). This was accompanied by a 21% reduction in plasma triglycerides (P < 0.01) and a 15% increase in high-density lipoprotein-2 cholesterol (P < 0.01) but there were no significant differences in total or low-density lipoprotein cholesterol. Conclusion: The antihypertensive and hypotriglyceridaemic effects of n-3 fatty acid supplementation seen in the present study suggest that it may be a useful adjunct to antihypertensive therapy with beta-blockers or diuretics.

Effects of dietary sodium and fish oil on blood pressure development in stroke-prone spontaneously hypertensive rats.

The postulated antihypertensive effect of dietary fish oil and the influence of dietary sodium on this effect were evaluated in young stroke-prone spontaneously hypertensive rats (SHRSP) by direct intra-arterial measurement of blood pressure. Weaning rats were fed synthetic diets containing olive oil or eicosapentaenoic acid-enriched fish oil (5% of dry weight) with normal (0.23%) or high (2.8%) sodium content. Catheters were implanted after 3 months for blood pressure measurement under resting conditions and to sample blood for catecholamine determinations. Effects of fish oil on vascular reactivity were assessed in the in situ blood-perfused mesentery. The overall observation, from a series of experiments, was that feeding diets containing 5% fish oil to young SHRSP resulted in a small but consistent suppression of the development of hypertension. This effect could be counteracted, however, by increasing dietary sodium intake. Observations after ganglion blockade indicate that the antihypertensive effect of fish oil is unlikely to result from a reduction in sympathetic vascular tone.

Blood pressure reduction by fish oil in adult rats with established hypertension — Dependence on sodium intake

The effects of fish oil combined with dietary sodium restriction on blood pressure and mesenteric vascular resistance were examined in a series of experiments with adult normotensive (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Rats were fed normal or low sodium diets containing fish oil, olive oil or safflower oil. Small but significant reductions of blood pressure (measured directly in conscious rats) were seen in SHRSP but not in WKY after 8 weeks on a fish oil/low sodium diet, compared with rats fed olive or safflower oil diets with normal sodium content. This antihypertensive effect was not dependent on neurally mediated vasoconstriction but was associated with a reduction of basal resistance in the blood-perfused mesenteric artery. Subcutaneous injection of fish oil reduced blood pressure in adult SHRSP on a normal sodium diet. However, there was a further fall in blood pressure when sodium intake was reduced. The results indicate the antihypertensive effect of fish oil can be enhanced by restricting sodium intake.

Evaluation of an omega-3 fatty acid supplement in diabetics with microalbuminuria

a CUR0 Division of Human Nutrition Adelaide SA 5000, Australia CDiabetes Clinic Modbury Hospital Modbury SA 5092, Australia dEndocrine and Diabetes Service m e Queen Elizabeth Hospital Woodville South SA 5011, Australia eAshjbrd Specialist Center Ashford SA 5035, Australia fDepartment of Chemical Pathology Womens and Childrens Hospital North Adelaide SA 5006, Australia JOHN J. GRAHAM,~ AND DAVID w. THO MAS^

Dietary Fish Oil Administration Retards Blood Pressure Development and Influences Vascular Properties in the Spontaneously Hypertensive Rat (SHR) but not in the Stroke Prone-Spontaneously Hypertensive Rat (SHR-SP)

In the present study, we compared the blood pressure in the SHR-SP and in the spontaneously hypertensive rat (SHR) after dietary administration of fish oil from 4 to 17 weeks of age. The retarding influence of dietary fish oils on the development of hypertension was prominent in the SHR (26 mmHg) and not evident in the SHR-SP (8 mmHg). The enhanced development of blood pressure in both the SHR and the SHR-SP is characterised by an elevated maximum contraction in the mesenteric vascular bed to sympathetic nerve stimulation and to injected noradrenaline. In SHR, but not SHR-SP, this maximum contraction was significantly attenuated by dietary fish oil. Likewise, acetylcholine mediated relaxation of the isolated aorta was enhanced in preparations from the SHR but not the SHR-SP. These physiological changes were also associated with a change in the total n-3 polyunsaturated fatty acids (PUFAs) content in vascular tissue, which were inversely proportional to the prevailing blood pressure values seen in all three strains of rat receiving dietary fish oils. Platelet activated thromboxane production was equally depressed in WKY (Wistar Kyoto), SHR and SHR-SP rats. The results indicate that the blood pressure lowering effect of fish oil when administered during the period of development of hypertension is much greater in the SHR than it is in the SHR-SP. Furthermore the lowering of blood pressure by fish oil administration is related to a restoration of normal vascular contraction and normal vascular relaxation, but not related to a suppression of serum thromboxane production.

Chronic central administration of enalaprilat lowers blood pressure in stroke-prone spontaneously hypertensive rats

Earlier studies on the cardiovascular effects of intracerebroventricular (i.c.v.) administration of angiotensin converting enzyme (ACE) inhibitors implicate angiotensin II (AII) present in the central nervous system in the pathogenesis of hypertension. We have now examined whether central AII contributes to the maintenance of established hypertension in adult stroke-prone spontaneously hypertensive rats (SHRSP). The ACE inhibitor, enalaprilat, was infused i.c.v. for two weeks at a rate of 5 micrograms/h via osmotic minipumps. Control rats were either untreated or infused with saline. Mean arterial pressure (MAP), measured via an indwelling catheter, fell within 24 h in the enalaprilat-treated rats and remained at least 30 mmHg lower than in controls. This difference persisted after intravenous (i.v.) administration of a vasopressin (AVP) antagonist but was eliminated by subsequent ganglion blockade with i.v. pentolinium. Without prior administration of the AVP antagonist, however, the reductions of MAP after pentolinium were smaller. The reduction was still attenuated in treated rats compared with controls but there was a significant difference in the residual MAP. Circulating catecholamine levels were reduced by central ACE inhibition. However, pressor responsiveness to i.v. phenylephrine was unaffected. The results suggest that, in SHRSP, central ACE inhibition lowers blood pressure by reducing sympathetic outflow, implying that central AII has a tonic sympathoexcitatory effect in this strain.

Effects of depleting central and peripheral adrenaline stores on blood pressure in stroke-prone spontaneously hypertensive rats.

The potential role of adrenaline, both circulating and in the central nervous system, in the maintenance of high blood pressure was examined in stroke-prone spontaneously hypertensive rats (SHRSP). alpha-Monofluoromethyldopa, a long-lasting inhibitor of dopa decarboxylase, was used to induce rapid depletion of central and peripheral catecholamine stores. Subsequent inhibition of phenylethanolamine-N-methyltransferase (PNMT) allowed the gradual restoration of dopamine and noradrenaline but not adrenaline, resulting in a greater relative depletion of adrenaline. Adrenaline was almost totally depleted in the circulation and peripheral tissues. The resting level of blood pressure, however, was unaffected, excepting after administration of a vasopressin (AVP) antagonist. Moreover, there was no reduction in the magnitude of acute pressor responses to electrical stimulation of the rostral ventrolateral medulla oblongata (C1 area), despite extensive loss of adrenaline from the brainstem and spinal cord. The results suggest that adrenaline contributes to the resting level of blood pressure but that its loss can be offset by the pressor activity of AVP. Thus neither central nor peripheral adrenaline stores appear to be essential for the maintenance of hypertension or for centrally-evoked vasoconstriction in adult SHRSP.