Docosahexaenoic acid restores endothelial function in children with hyperlipidemia: results from the EARLY study.

OBJECTIVE: The primary objective of this study was to determine whether the National Cholesterol Education Program Step II (NCEP-II) diet or supplementation with docosahexaenoic acid (DHA) with the diet, affects endothelial function in children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). As secondary endpoints, the influence of diet and DHA supplementation on lipid profiles as well as biomarkers for oxidative stress and inflammation, and asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, were all evaluated. METHODS: In a double-blind, placebo-controlled, randomized, crossover study design, 20 children (ages 9-19 years) with FH (n = 12) and FCH (n = 8) received nutritional counseling based on the National Cholesterol Education Program Step II (NCEP-II) and food guide pyramid dietary guidelines for 6 weeks. They were then randomly assigned to supplementation with docosahexaenoic acid (DHA 1.2 g/d) or placebo for 6 weeks, followed by a washout phase of 6 weeks and crossover phase of 6 weeks while continuing the NCEP-II diet. Endothelium-dependent flow-mediated dilation (FMD) of the brachial artery was determined by high-resolution ultrasound. Plasma levels of total cholesterol, triglycerides and lipoprotein classes (LDL, HDL, VLDL) were measured by ultracentrifugation and enzymatic methods, plasma F2 isoprostanes by gas chromatography/mass spectrometry, urinary 8-OH-2' deoxyguanosine by liquid chromatography, high sensitivity C-reactive protein by immunonephelometry and ADMA by liquid chromatography. RESULTS: FMD increased significantly after DHA supplementation compared to baseline (p < 0.001), diet alone (p < 0.002), placebo (p < 0.012) and washout (p < 0.001) phases of the study without affecting biomarkers for oxidative stress, inflammation or ADMA. DHA supplementation was associated with increased levels of total cholesterol (p < 0.01), LDL- and HDL cholesterol concentrations (p < 0.001) compared to the NCEP-II diet. CONCLUSION: This study demonstrates that DHA supplementation restores endothelial-dependent FMD in hyperlipidemic children. The endothelium may thus be a therapeutic target for DHA. This is consistent with a hypothesis of increasing NO bioavailability, with the potential for preventing the progression of early coronary heart disease in high-risk children.

Dietary docosahexaenoic acid affects stearic acid desaturation in spontaneously hypertensive rats.

Docosahexaenoic acid (DHA, 22:6n-3) is an n-3 polyunsaturated fatty acid which attenuates the development of hypertension in spontaneously hypertensive rats (SHR). The effects of DHA on delta-9-desaturase activity in hepatic microsomes and fatty acid composition were examined in young SHR. Two groups of SHR were fed either a DHA-enriched diet or a control diet for 6 wk. Desaturase activity and fatty acid composition were determined in hepatic microsomes following the dietary treatments. Delta-9-desaturase activity was decreased by 53% in DHA-fed SHR and was accompanied by an increase in 16:0 and a reduction in 16:1n-7 content in hepatic microsomes. The DHA diet also increased the levels of eicosapentaenoic acid (20:5n-3) and DHA. The n-6 fatty acid content was also affected in DHA-fed SHR as reflected by a decrease in gamma-linolenic acid (18:3n-6), arachidonic acid (20:4n-6), adrenic acid (22:4n-6), and docosapentaenoic acid (22:5n-6). A higher proportion of dihomo-gamma-linolenic acid (20:3n-6) and a lower proportion of 20:4n-6 is indicative of impaired delta-5-desaturase activity. The alterations in fatty acid composition and metabolism may contribute to the antihypertensive effect of DHA previously reported.

Mechanisms of vasorelaxation induced by eicosapentaenoic acid (20:5n-3) in WKY rat aorta.

The vasorelaxant activity of eicosapentaenoic acid (EPA, 20:5n-3), the omega-3 polyunsaturated fatty acid, was investigated in isolated Wistar Kyoto (WKY) rat aortae by measuring isometric tension. Eicosapentaenoic acid (1 - 100 microM) relaxed rat aortae contracted with high K(+) (80 mM) or noradrenaline (NA, 1 microM) in a concentration-dependent manner. Contractions induced by Bay K 8644 or increasing concentrations of calcium were unaffected by EPA. The relaxant effect of EPA (3 - 100 microM) was significantly inhibited by indomethacin (10 microM), the cyclo-oxygenase inhibitor, but not by the nitric oxide (NO) synthesis inhibitor, N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME, 100 microM). Removal of the endothelium did not alter EPA-induced relaxations. In Ca(2+)-free, EGTA 2 mM solution, EPA (10 - 30 microM significantly inhibited NA-sustained contractions. Incubation with EPA (5, 10 microM) diminished both NA-induced (1 microM) phasic and sustained contractions. The vasorelaxant effects of EPA (> or =30 microM) on NA-induced (1 microM) contractions were significantly inhibited by the K(+) channel blocker, glibenclamide (10 microM), but not tetraethylammonium (1 mM). Moreover, indomethacin and glibenclamide combined significantly inhibited EPA-induced (1 - 100 microM) responses. These results indicate EPA exerts its endothelium-independent vasorelaxant effects in WKY rat aortae through production of prostanoids which activate K(+)(ATP) channels. Inhibition of Ca(2+) mobilization from intracellular pools and influx through the non-L-type, but not the L-type, Ca(2+) channel are also possible mechanisms action of EPA's.

Docosahexaenoic acid--induced vasorelaxation in hypertensive rats: mechanisms of action.

The authors investigated the vasorelaxant properties of the omega-3 fatty acid, docosahexaenoic (DHA, 22:6n-3), and the possible involvement of endothelium-derived nitric oxide, prostanoids, opening of K+ channels, and/or modulation of calcium-mediated events. Isolated aorta from male spontaneously hypertensive rats (SHR) (age 16-17 weeks) were used to measure isometric tension. DHA-induced (1-100 mumol/l) relaxation was examined following contraction to norepinephrine (NE) (10(-6) mol/l) or high-K+ (80 mmol/l) solution in the presence and absence of various inhibitors and calcium-containing solution. DHA acid induced a significant vasorelaxant effect in both NE and high-K(+)-induced contracted SHR aortic rings, although DHA relaxations were greater in high-K(+)-induced contracted rings. In the absence of extracellular calcium, DHA (5-30 mumol/l) inhibited the initial phasic and sustained components of NE-induced contraction under different conditions. Inhibition of nitric oxide synthesis by N omega-nitro-L-arginine methyl ester hydrochloride (100 mumol/l) had no effect on DHA relaxations; however, indomethacin or nifedipine caused significant inhibition at > or = 30 mumol/l DHA. The K+ channel blocker, glibenclamide, but not tetraethyl-ammonium, also had an inhibitory effect on DHA-induced relaxation. These results indicate that DHA's vasorelaxant actions in SHR aorta are independent of endothelium-derived nitric oxide; however, at DHA concentrations > or = 30 mumol/l, vasodilatory prostanoids that activate ATP-sensitive K+ channels (KATP) may be involved. At lower concentrations, DHA-induced relaxation appears to be attributed to modulation of intracellular Ca2+ release and L-type Ca2+ channels in vascular smooth muscle cells. The vasorelaxant properties of DHA may contribute, in part, to the blood pressure-lowering effect of dietary fish oil in this hypertensive model.

Docosahexaenoic acid is an antihypertensive nutrient that affects aldosterone production in SHR.

The effects of dietary docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid, on blood pressure and some pressure-regulating systems were measured in young spontaneously hypertensive rats (SHR). Plasma aldosterone and corticosterone levels, adrenal aldosterone production in vitro, and characteristics of adrenal angiotensin receptors were measured after 6 weeks of diet. Renal cytochrome P450 (CYP) 4A gene expression and arachidonic acid metabolism by renal microsomes were also investigated. Plasma cholesterol, triglycerides, and high-density lipoprotein cholesterol were measured. Diets contained either corn/soybean oil alone (CSO), or oil enriched with DHA. After 6 weeks, rats fed DHA had systolic blood pressures averaging 34 mmHg less than controls (P < 0.001). Plasma aldosterone levels were 33% lower in the DHA-fed animals than in controls (22 +/- 3 vs. 33 +/- 3.7 ng/dl, P < 0.05). Plasma levels of corticosterone were 18% lower in animals fed DHA than in controls, but this difference was not statistically significant. Adrenal glomerulosa cells from DHA-fed rats produced less aldosterone in vitro in response to angiotensin II, ACTH, or potassium. The difference was less marked when aldosterone production was stimulated by supplying exogenous corticosterone, suggesting an effect of DHA on postreceptor steps in signal transduction or the early pathway of aldosteronogenesis. We found no significant differences in angiotensin receptor subtype, number, or affinity. Production of arachidonic epoxides by renal microsomes was 17% lower in DHA-fed animals than in controls (P < 0.05). Renal cortical mRNA levels of CYP4A genes and formation of 19- and 20-hydroxyeicosatetraenoic acid (HETE) did not differ between dietary groups. Plasma total cholesterol and high-density-lipoprotein (HDL) levels were significantly reduced in SHR fed the DHA supplement, but triglyceride levels were not significantly different. The effects of DHA on steroid and eicosanoid metabolism may be part of the mechanism by which this fatty acid prevents some of the hypertension in growing SHR.

Calcium-mediated mechanisms of eicosapentaenoic acid-induced relaxation in hypertensive rat aorta.

We have previously demonstrated the vasorelaxant properties of the omega-3 fatty acid, eicosapentaenoic acid (EPA), in normotensive and spontaneously hypertensive rat (SHR) aorta, although the mechanism(s) of action are not fully understood. Because endothelial dysfunction and increased intracellular free calcium concentration ([Ca2+]i) are seen in hypertensive rat aorta, we investigated the potential role of Ca2+ signaling, endothelium and derived factors, and the opening of potassium (K+) channels in EPA-induced relaxation. In the presence of extracellular Ca2+, EPA induced significant relaxations at >10 micromol/L (P<.01) in norepinephrine (NE) (10(-6) mol/L)-contracted aortic rings and at 30 micromol/L (P<.001) in high K+ (80 mmol/L)-contracted aortic rings. In the absence of extracellular Ca2+, EPA (10 to 30 micromol/L) inhibits the tonic component of NE-induced contraction (P<.0001). The relaxant properties of EPA in SHR aorta appear specific to Ca2+ release from an internal storage site associated with NE-induced tonic contraction. Further studies with the use of fura-2 to measure [Ca2+]i in cultured vascular smooth muscle (VSM) cells from SHR aorta indicated that EPA (30 micromol/ L)-pretreatment attenuated angiotensin II (50 nmol/ L)-induced Ca2+ transient by 95%, suggesting that an inhibitory effect on the Ca2+ signaling may underlie EPA-induced relaxation of the vessel preparation. In addition, EPA per se induced an increase in [Ca2+li with a duration of approximately 20 min in VSM cells, and the effect was not altered by removal of extracellular Ca2+. There was no increase in the level of inositol-1,4,5-trisphosphate in response to EPA (30 micromol/L). The actions of EPA are independent of endothelium-derived factors, cyclooxygenase metabolites, and activation of K+ channels since endothelium removal, N(omega)-nitro-L-arginine methyl ester hydrochloride, (L-NAME, 100 micromol/L), indomethacin (10 micromol/L), tetraethylammonium (1 mmol/L), and glibenclamide (10 micromol/L) did not affect EPA-induced vasodilation in NE-precontracted aortic rings. These results suggest that EPA directly modulates intracellular Ca2+ signaling in VSM cells, and that this may contribute to the vasorelaxant effect and, at least in part, the blood pressure-lowering effect of fish oil.

The effects of a diet rich in docosahexaenoic acid on organ and vascular fatty acid composition in spontaneously hypertensive rats.

Previous research has shown that dietary docosahexaenoic acid (DHA) attenuates the development of high blood pressure in young spontaneously hypertensive rats (SHR). The purpose of this study was to investigate the effects of dietary DHA on organ and vascular fatty acid composition in SHR. Given the important structural and functional role of fatty acids in cell membranes, alterations in fatty acid composition may contribute to the antihypertensive effect of DHA. SHR were fed a purified diet containing either a corn/soybean oil mixture (CSO, control) or a DHA-enriched oil for 6 weeks. The DHA diet markedly increased the levels of DHA in the aorta, renal artery, plasma, liver, heart, kidney, and lung by 5-, 15-, 7-, 6-, 3.8-, 3.5-, and 8.8-fold (P<0.001), respectively. The levels of eicosapentaenoic acid were also increased while there was a concomitant reduction in arachidonic and adrenic acids. Therefore, dietary DHA increases the incorporation of omega-3 polyunsaturated fatty acids in specific organs and vascular tissue in SHR at the expense of omega-6 polyunsaturated fatty acids.

Dietary borage oil alters plasma, hepatic and vascular tissue fatty acid composition in spontaneously hypertensive rats.

Dietary borage oil rich in gamma-linolenic acid (GLA) has been shown to lower blood pressure in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). A potential mechanism for this effect may be attributed to changes in metabolism of GLA to dihomogamma-linolenic (DGLA) and arachidonic acids (AA). We investigated the effects of dietary borage oil on fatty acid composition in the plasma, liver and vascular tissue in WKY and SHR. The diet significantly increased the levels of omega-6 polyunsaturated fatty acids. GLA and DGLA levels in the plasma, liver, aorta and renal artery tissues increased in SHR (P < 0.001) and WKY (P < 0.001). AA levels were also increased in both plasma and liver of SHR (P < 0.05) and WKY (P < 0.05) fed the borage oil enriched diet. The results demonstrate that dietary borage oil produces marked changes in the metabolism of GLA which may contribute to its blood pressure lowering effect in WKY and SHR.

Effects of dietary gamma-linolenic acid on blood pressure and adrenal angiotensin receptors in hypertensive rats.

In a previous study, we showed that dietary gamma-linolenic acid (GLA), an omega-6 polyunsaturated fatty acid found in borage oil (BOR), attenuates the development of hypertension in young spontaneously hypertensive rats (SHR). The purpose of this study was to determine the effects of dietary GLA on established hypertension in adult rats, as well as its effects on components of the renin-angiotensin-aldosterone axis. For 5 weeks, male SHR (14-15 weeks old) were fed a basal fat-free diet to which 11% by weight of sesame oil (SES) or BOR was added. Systolic blood pressure (SBP), determined by the tail cuff method, and weight were measured weekly. Plasma renin activity (PRA), aldosterone (PA), and corticosterone (PC) levels were measured at the end of the dietary treatments. The adrenal glands were homogenized, and angiotensin II (ANG II) binding was measured and plotted according to Scatchard. Systolic blood pressure was 12 mmHg lower at Week 5 in SHR fed the BOR diet compared to SES-fed rats (P < 0.005). Weight gains were similar in both dietary groups. Plasma aldosterone was lower, PRA was higher, and the PA/PRA ratio was significantly lower (P < 0.05) in BOR-fed rats. Levels of PC were the same in both groups. The BOR-enriched diet reduced adrenal ANG II receptor density and affinity compared to the SES diet. Results suggest that BOR inhibits adrenal responsiveness to ANG II by an action on adrenal receptors. Our findings demonstrated that dietary GLA lowers SBP in adult SHR. This effect may be mediated, at least in part, by interference with the renin-angiotensin-aldosterone system at the level of adrenal ANG II receptors.

Age-related changes in plasma and tissue fatty acid composition in Fischer 344 rats.

Advancing age is associated with increased risk of coronary artery disease. Changes in fatty acid metabolism affect important cellular membrane properties and functions which may contribute to the vascular pathophysiology of aging. This study was designed to investigate the effects of aging on the fatty acid composition of the plasma, liver, aorta, and renal artery in 4-, 15-, and 24-month old Fischer 344 rats, an animal model for aging. With aging, the levels of total polyunsaturated fatty acids (PUFA) increased in the plasma, aorta, and renal artery. The major changes in the liver fatty acid profile were increases in the levels of 18:2n6 and 18:3n3 and a decrease in the levels of 20:3n6 and 20:5n3. The results indicate that significant shifts occur in the levels of n6 and n3 PUFA in the plasma, liver, and vasculature with aging. The alterations in the fatty acid composition may be a pathogenetic mechanism of the vascular changes associated with aging.

Influence of aging on the relaxant responses to omega-3 fatty acids in Fischer 344 rat aorta.

The effect of age on the vasorelaxant properties of the omega-3 fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA), in isolated rat aortic rings were investigated in 4-, 15- and 24-month-old Fischer 344 rats. Increased aortic wall thickness was seen in both 15- and 24-month-old rats. Maximal contractile responses to norepinephrine (NE) were greater in intact and de-endothelialized (ENDO-) rings from 15- and 24-month-old rats; although increased sensitivity to NE was exhibited in 4-month-old rings. DHA- and EPA-induced (1-100 mumol/l) responses were similar between the three age groups in intact rings. Removal of the endothelium enhanced relaxant responses to both DHA and EPA in all three groups. EPA-induced (1-100 mumol/l) responses ranged from-4 to 28% for both 4- and 15- month ENDO- rings and -1 to -18% in 24-month ENDO-rings. DHA ENDO-ring responses (1-100 mumol/l) were- 4 to -13% in 4 months, -5 to -23% in 15 months, and -0.8 to -16% in 24 months. Age differences were apparent with the ENDO- ring responses to DHA and EPA. These differences were seen with greater relaxant responses to both EPA and DHA in the 4- and 15-month-old aortic rings. Increased sensitivity and a greater maximal relaxant response to acetylcholine (ACH) was noted in the 15-month-old group. Four- and 24-month rings exhibited similar sensitivity and maximal relaxant responses to ACH. However, relaxation was decreased in 24-month rings at low ACH concentrations. These findings suggest that both functional and morphological changes occur with aging. DHA- and EPA-induced responses are not altered by aging in intact rings; however, removal of the endothelium enhances their vasorelaxant properties in all three age groups. This may be related to the direct actions of DHA and EPA on vascular smooth muscle, rather than on mechanisms associated with generation of endothelium-derived relaxing factor.

Assessment of the cardiovascular effects of stress.

The stress response increases sympathetic nervous activity, which can adversely affect the cardiovascular system. Cardiovascular disease is due in part to stress-induced mechanisms mediated primarily through increased adrenergic stimulation. These stress-induced mechanisms include elevations in serum lipid levels, alterations in blood coagulation, atherogenesis, vascular changes in hypertension, and myocardial ischemia. Stress management interventions for hypertension are controversial; however, interventions for coronary heart disease-prone behavior patterns have proven successful. Stress management interventions have also reduced cardiovascular events, mortality, and coronary atherosclerosis. Assessment of stress includes individual interviews, which can be complemented by information derived from questionnaires and mental stress testing. Educational and relaxation strategies can prepare patients to understand and cope with stress. These approaches will hopefully decrease the occurrence of stress and, ultimately, the risk for cardiovascular disease.

Vasorelaxant properties of n-3 polyunsaturated fatty acids in aortas from spontaneously hypertensive and normotensive rats.

BACKGROUND: Dietary consumption of fish, rich in n-3 polyunsaturated fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), has been shown to reduce blood pressure in both animal studies and clinical trials. Although the antihypertensive mechanisms are not known, the blood-pressure-lowering effect of n-3 polyunsaturated fatty acids may be partially attributed to their vasorelaxant properties. METHODS: Aortic rings with and without endothelium, from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR), 16-17 weeks old, were suspended in tissue baths and isometric tension was measured. Concentration-response curves were generated for DHA and EPA (1-100 mu mol/l) in norepinephrine-contracted rings. Blood pressure was measured using the tail-cuff method and aortic media thickness was determined. RESULTS: Blood pressure was significantly increased in SHR (n=10; 194 +/- 4.4 mmHg) compared with WKY (n=10; 124 +/- 1.2 mmHg, P < or = 0.0001). DHA (1-100 mu mol/l) relaxed aortic rings f rom WKY (-3.3 +/- 0.7 to -13 +/- 2.3%, P < or = 0.001) and from SHR (-6.5 +/- 1.8 to -22.9 +/- 4%, P < or = 0.01) in a concentration-dependent manner. EPA (1-100 mu mol/l) evoked greater relaxation in SHR (-10.1 +/- 2.0 to -33 +/- 3.9%, P < 0.01) than in WKY (-2.9 +/- 1.1 to -18.3 +/- 2.1%, P < 0.01) aortic rings. The relaxant effect of DHA in both WKY and SHR and of EPA in WKY were not dependent on an intact endothelium. However, EPA (1-10 mu mol/l) induced greater responses in intact SHR rings (-10.1 +/- 2.0 to -14.5 +/- 3.1%) than in de-endothelialized SHR rings (0 to -2.1 +/- 1.7%, P = 0.001). CONCLUSION: The direct relaxant effects of n-3 fatty acids as seen in WKY and SHR may contribute, in part, toward the blood-pressure-lowering effect of dietary fish and fish-oil supplementation.

Vascular effects of omega-3 fatty acids: possible therapeutic mechanisms in cardiovascular disease.

Dietary consumption of omega-3 polyunsaturated fatty acids (PUFAs) found in seafood and fish oils is associated with a decrease in coronary heart disease and overall cardiovascular mortality. Omega-3 PUFAs exert a number of physiologic effects, including relaxation of vascular smooth muscle, lowering of blood pressure, interference in phosphatidylinositol signaling, a reduction in platelet aggregation and growth factors, a decrease in atherogenic lipoproteins, a reduction in thrombotic factors, alterations in eicosanoid metabolism, a decrease in platelet and macrophage activating factors, and an increase in thrombolytic substances. These factors may provide a therapeutic means of reducing cardiovascular disease. This article reviews the vascular effects of omega-3 PUFAs and discusses the hypolipidemic, antihypertensive, antiatherosclerotic, antiinflammatory, and antithrombotic actions of the omega-3 PUFAs. Specific nursing implications are addressed.

Exploratory data analysis of hyperlipidemia on the Macintosh: software tools for analysis of biochemical, clinical, and genetic variables in 1677 consecutive lipid clinic patients.

Exploratory data analysis (EDA) software facilitates unstructured, iterative open exploration of complex datasets with the aid of multiple linked graphical displays. We are investigating relationships between plasma lipoproteins and coronary artery disease by retrospective analysis of 1677 consecutive UCSF Lipid Clinic patients. Our preliminary experience is with Data Deck 3.0 although several additional software programs (JMP 2.0, Systat 5.1, Minitab 8.0, StatView 4.0) are mentioned. Lipid diagnosis (751 women and 925 men) was 22% primary hypercholesterolemia, 19% combined hyperlipidemia, 3% dysbetalipoproteinemia, 15% endogenous lipemia, 4% mixed lipemia, 5% elevated Lp(a) and 32% with no major lipid abnormality. We found the Macintosh platform (68030) to be flexible and powerful for analysis of moderate size (less than 1 Mb) clinical datasets. High resolution color monitors (1024 x 768 pixels), fast hard disks (< 18 msec) and moderate amounts of system memory (8 + Mb) facilitate exploratory analysis.

Vascular relaxation to omega-3 fatty acids: comparison to sodium nitroprusside, nitroglycerin, papaverine, and D600.

The vasorelaxant activity of the omega-3 fatty acids--docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids--in comparison with other known vasodilators--sodium nitroprusside, nitroglycerin, papaverine, and D600--were studied in the isolated rat aorta. The relaxant responses of these vasodilators and fatty acids at concentrations of 1-100 microM were assessed in aortic rings contracted with norepinephrine (NE 10(-6) M) or with KCl (30 mM). Cyclic nucleotide enhancers (sodium nitroprusside, nitroglycerin, papaverine) were more effective in producing relaxation, regardless of the contractile mechanism, i.e., alpha-adrenoceptor stimulation or depolarization. In contrast, the omega-3 fatty acids produced augmented relaxation in NE-contracted vessels. Relaxations produced by DHA (15 +/- 2% to 45 +/- 10%) were similar to D600 (16 +/- 2% to 60 +/- 7%) in NE-contracted rings, but not in KCl contracted rings. The responses to D600 and DHA in KCl-contracted vessels were 79 +/- 2% to 104 +/- 3% and 5 +/- 1% to 21 +/- 3%, respectively. In another set of experiments, the effects of omega-3 fatty acids in the presence of albumin were examined; no significant differences in the induced relaxant responses were noted. These results suggest that the mechanisms of vascular relaxation, such as cyclic nucleotide elevation and calcium antagonism of potential-operated channels, are different from those induced by the omega-3 fatty acids.

Cardiovascular disease prevention: knowledge and attitudes of graduate nursing students.

Graduate nursing students were surveyed to determine the knowledge and attitudes of cardiovascular disease prevention. Questionnaires were self-administered to first-year graduate nursing students (n = 50) in a school of nursing prior to and following a physiology course with cardiovascular disease prevention content. In general, the results demonstrated that the respondents were least knowledgeable regarding the prevalence of smoking, the gender differences in high-density lipoprotein (HDL)-cholesterol levels, the influence of body weight on lipids and the recommended percentages of calories from dietary fat. A significant improvement in knowledge was noted after the course. Positive attitudes regarding the importance of cardiovascular disease prevention and the partnership between patients and clinicians necessary to manage risk were identified. These attitudes did not change significantly following the course. These results indicate that graduate education which emphasizes cardiovascular disease prevention increases knowledge. Coupled with positive attitudes and healthy personal lifestyle behaviours, knowledge of cardiovascular disease prevention may enhance the ability of nurses to integrate preventive standards into clinical practice and ultimately decrease the risk of cardiovascular disease.

Dietary gamma-linolenic acid lowers blood pressure and alters aortic reactivity and cholesterol metabolism in hypertension.

OBJECTIVE: To determine the effects of dietary gamma-linolenic acid upon blood pressure, aortic reactivity and cholesterol metabolism in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. DESIGN: Randomized parallel-group study. METHODS: SHR and WKY rats were fed a purified diet containing either sesame or borage oil rich in gamma-linolenic acid for 7 weeks. Blood pressure measured by the tail-cuff method and weight were monitored weekly. At the end of the study, intra-arterial pressor responses to norepinephrine and angiotensin II, and reactivity of isolated aortic rings to norepinephrine, angiotensin II, KCl and acetylcholine were determined. Serum cholesterol and triglycerides were measured. Hepatic and intestinal enzymes and receptors of cholesterol metabolism were also measured. RESULTS: Dietary borage oil significantly decreased blood pressure in SHR and WKY rats compared with sesame oil-fed rats. Pressor responses to norepinephrine and angiotensin II, and aortic reactivity to norepinephrine, angiotensin II, KCl and acetylcholine were not significantly different. The borage oil diet increased serum cholesterol levels in WKY rats and hepatic B-hydroxy-3-methylglutaryl coenzyme A reductase in SHR. CONCLUSION: These data indicate that dietary borage oil has a blood pressure lowering effect in hypertensive and normotensive rats. However, the effect cannot be explained by altered sensitivity to humoral and neural vasoconstrictors or changes in cholesterol metabolism. Other mechanisms should be investigated.

Effect of omega-3 fatty acids, docosahexaenoic and eicosapentaenoic, on norepinephrine-induced contractions.

The relaxant responses of the rat thoracic aorta to omega-3 fatty acids, docosahexaenoic and eicosapentaenoic, on norepinephrine- and potassium-induced contractions were investigated. Relaxation was enhanced in vessels contracted with norepinephrine. Docosahexaenoic acid at concentrations as low as 1, 3, and 10 microM evoked significant relaxant responses (15, 23, 30%) in norepinephrine-contracted vessels as compared with responses (5, 9, 12%) in potassium-contracted vessels. Results for eicosapentaenoic acid under similar conditions were 3, 8, and 19% in norepinephrine-contracted vessels and 3, 3, and 8% in potassium-contracted vessels. Pretreatment with eicosapentaenoic (10 microM) or docosahexaenoic acids (1-10 microM) decreased the contractile response to physiologic concentrations of norepinephrine. In the presence of calcium-free medium, the omega-3 fatty acids (1-30 microM) significantly abolished sustained norepinephrine contractions but did not reduce the phasic contractions when incubated prior to norepinephrine contraction. Comparatively, the effects of docosahexaenoic acid were greater than eicosapentaenoic acid. These findings suggest that the relaxant effects of the omega-3 fatty acids are specific to the mode of contraction, i.e., alpha-adrenoceptor stimuli. This effect may be related to intracellular calcium mechanisms, since both fatty acids reversed norepinephrine-induced sustained contractions in the absence of extracellular calcium.