Since 1980, the American College of Cardiology (ACC) and American Heart Association (AHA) have translated scientific evidence into clinical practice guidelines (guidelines) with recommendations to improve cardiovascular health. In 2013, the National Heart, Lung, and Blood Institute (NHLBI) Advisory

http://kidneys.zaslavsky.com.ua/article/download/122220/118980

2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000597

Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events.

Oxygenated derivatives of cholesterol (oxysterols) present a remarkably diverse profile of biological activities, including effects on sphingolipid metabolism, platelet aggregation, apoptosis, and ...

Oxysterols: modulators of cholesterol metabolism and other processes.

The MAPK cascades: Signaling components, nuclear roles and mechanisms of nuclear translocation

Flaxseed contains ω-3 fatty acids, lignans, and fiber that together may provide benefits to patients with cardiovascular disease. Animal work identified that patients with peripheral artery disease may particularly benefit from dietary supplementation with flaxseed. Hypertension is commonly associated with peripheral artery disease. The purpose of the study was to examine the effects of daily ingestion of flaxseed on systolic (SBP) and diastolic blood pressure (DBP) in peripheral artery disease patients. In this prospective, double-blinded, placebo-controlled, randomized trial, patients (110 in total) ingested a variety of foods that contained 30 g of milled flaxseed or placebo each day over 6 months. Plasma levels of the ω-3 fatty acid α-linolenic acid and enterolignans increased 2- to 50-fold in the flaxseed-fed group but did not increase significantly in the placebo group. Patient body weights were not significantly different between the 2 groups at any time. SBP was ≈ 10 mm Hg lower, and DBP was ≈ 7 mm Hg lower in the flaxseed group compared with placebo after 6 months. Patients who entered the trial with a SBP ≥ 140 mm Hg at baseline obtained a significant reduction of 15 mm Hg in SBP and 7 mm Hg in DBP from flaxseed ingestion. The antihypertensive effect was achieved selectively in hypertensive patients. Circulating α-linolenic acid levels correlated with SBP and DBP, and lignan levels correlated with changes in DBP. In summary, flaxseed induced one of the most potent antihypertensive effects achieved by a dietary intervention.

Potent Antihypertensive Action of Dietary Flaxseed in Hypertensive Patients

Flaxseed is a rich source of the omega-3 fatty acid, alpha linolenic acid, the lignan secoisolariciresinol diglucoside and fiber. These compounds provide bioactivity of value to the health of animals and humans through their anti-inflammatory action, anti-oxidative capacity and lipid modulating properties. The characteristics of ingesting flaxseed or its bioactive components are discussed in this article. The benefits of administering flaxseed or the individual bioactive components on health and disease are also discussed in this review. Specifically, the current evidence on the benefits or limitations of dietary flaxseed in a variety of cardiovascular diseases, cancer, gastro-intestinal health and brain development and function, as well as hormonal status in menopausal women, are comprehensive topics for discussion.

https://www.mdpi.com/2072-6643/11/5/1171/pdf

Dietary flaxseed as a strategy for improving human health

Objective: The aim was to examine the regulation of the cardiac Na+/H+ exchanger NHE-1 isoform mRNA in response to ischaemia and acidosis in the mammalian myocardium. Methods: Male Sprague Dawley rat hearts were perfused in a non-circulated retrograde fashion according to the Langendorff method. Hearts were perfused for 3 h at flow rates of either 10 ml·min−1 (control), or 3, 1, or 0 ml·min−1 (ischaemia) followed by 5 min of reperfusion. Hearts were immediately frozen in liquid N2, and stored at −80 °C until ready for RNA isolation. Northern blot analysis was used to examine expression of the NHE-1 isoform of the Na+/H+ exchanger message in these isolated perfused hearts. Activity of the Na+/H+ exchanger was assessed in primary cultures of neonatal rat myocytes under either control conditions or after treatment with chronic, low external pH. Results: A decrease in developed tension and an increase in resting tension was observed which was dependent upon the severity of the ischaemic episode. Low flow ischaemia of 3 ml·min−1 caused increased Na+/H+ exchanger message levels, while perfusion at more reduced flow rates eliminated the increase. Treatment of primary cultures of isolated myocytes with low external pH resulted in increased ability to recover from an acute acid load. Conclusions: Low flow ischaemia can increase the Na+/H+ exchanger message in the intact mammalian myocardium. More severe ischaemia prevents the increase, suggesting that severely damaged tissue may not be capable of the ischaemic response. Primary cultures of isolated myocytes can respond to chronic low external pH by increasing Na+/H+ exchanger activity.

Induction of expression of the sodium-hydrogen exchanger in rat myocardium

The purpose of the present study was to compare the protective effects of amiloride and three of its derivatives (which are selective inhibitors of Na(+)-H+ exchange) during postischemic reperfusion. Previously, amiloride has been shown to have a protective effect on ischemia-reperfusion injury. However, because of its nonselective actions, the mechanism of its effect is unclear. 5-(N,N-dimethyl)-amiloride (DMA) is also protective and appears to act via inhibition of the Na(+)-H+ exchanger. However, corroborative effects using other selective Na(+)-H+ exchange blockers are needed. Amiloride, DMA, ethylisopropyl amiloride (EIPA), and 5-(N,N-hexamethylene)-amiloride (HMA) were included for 10 min in the reperfusion period after 60 min of global ischemia in the rat right ventricular wall. Peak developed tension and the rates of tension generation and relaxation were significantly improved during reperfusion in the presence of 100 microM amiloride, 10 microM DMA, 2.5 microM HMA, or 1 microM EIPA compared with those of drug-untreated muscles. Contracture formation was significantly depressed in the presence of these drug concentrations as was release of creatine kinase from the ventricular wall into the coronary effluent. The efficacy of these drugs for protecting the right ventricular wall from postischemic contractile dysfunction correlates well with their potency as blockers of Na(+)-H+ exchange. The results provide further evidence in support of a role for Na(+)-H+ exchange. The results provide further evidence in support of a role for Na(+)-H+ exchange in determining ischemia-reperfusion injury in the heart.

Effect of amiloride and selected analogues on postischemic recovery of cardiac contractile function.

Amiloride and its derivatives (benzamil, dichlorobenzamil, 5-(N,N-dimethyl)-amiloride, 5-(N-ethyl-N-isopropyl)-amiloride, (N,N-hexamethylene)- amiloride and 5-(N-methyl-N-isobutyl)-amiloride) are commonly used as selective blockers of Na+/Ca++ exchange or Na+/H+ exchange. Very little information is currently available regarding their effects on cardiac performance. It was observed that addition of amiloride or any of the selected derivatives to the coronary perfusate of the right ventricular wall produced a potent depressive effect on peak developed tension and the rates of tension generation and dissipation. The concentrations at which this occurred are those that are commonly used in ischemia or hypoxia studies. Significantly, the depressive action of the drugs increased with the perfusion duration and never achieved a stable level. An initial, transient positive inotropic effect was observed with some of the drugs. If the drug concentration and perfusion time was limited, the effects were reversible. All of the drugs except amiloride produced extra systoles. The drugs were capable of blocking Ca++ transients in isolated cardiomyocytes but had little effect on intracellular pH. The drugs lengthened the action potential duration and decreased the action potential amplitude and upstroke velocity. Their effects on cardiac performance may involve a complex inhibition of Ca++ influx and K+ efflux in addition to a stimulation of a nonselective cation current. It is concluded that amiloride and its analogs have striking effects on cardiac performance which may be unrelated to their capacity to inhibit Na+/Ca++ or Na+/H+ exchange. In summary, the use of these drugs is not normally recommended in cell or tissue perfusion experiments because of their nonselectivity. However, if the drug concentration and perfusion time is controlled carefully, interpretable data may be obtained in some cases.

Thane G. Maddaford

Papers

Potent Antihypertensive Action of Dietary Flaxseed in Hypertensive Patients

Dietary flaxseed as a strategy for improving human health

Induction of expression of the sodium-hydrogen exchanger in rat myocardium

Effect of amiloride and selected analogues on postischemic recovery of cardiac contractile function.

Modulation of cardiac performance by amiloride and several selected derivatives of amiloride.