Carol Ann Ford

Dietary α-lipoic acid supplementation lowers blood pressure in spontaneously hypertensive rats.

Background and objectives In spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, α-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs. Methods and results Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar-Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Conclusions Dietary α-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.

Role of aldehydes in fructose induced hypertension

Aldehydes are formed in tissues of humans and animals as intermediates of glucose and fructose metabolism and due to lipid peroxidation. N-acetyl cysteine (NAC), an analogue of the dietary amino acid cysteine, binds aldehydes thus preventing their damaging effect on physiological proteins. We measured systolic blood pressure (SBP), platelet cytosolic free calcium [Ca2+]i and tissue aldehyde conjugates in fructose induced hypertensive Wistar-Kyoto (WKY) rats and examined the effect of NAC in the diet on these parameters. Animals age 7 weeks were divided into three groups of 6 animals each and were treated as follows: WKY-control (chow diet and normal drinking water); WKY-Fructose (chow diet and 4% fructose in drinking water); WKY-Fructose+NAC (1.5% NAC in chow diet and 4% fructose in drinking water). After 11 weeks, systolic blood pressure, platelet [Ca2+]i and kidney aldehyde conjugates were all significantly higher in fructose treated rats. NAC treatment prevented these changes. These results suggest that aldehydes may be the cause of fructose induced hypertension and elevated cytosolic free calcium.

Dietary vitamin C supplementation lowers blood pressure in spontaneously hypertensive rats

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. Vitamin C can increase tissue cysteine and glutathione levels. The aim of the present study was to investigate whether a dietary supplementation of vitamin C can lower tissue aldehydes and blood pressure and normalize associated biochemical and histopathological changes in SHRs. Starting at 12 weeks of age, animals were divided into 3 groups of 6 animals each. Animals in the WKY-control group and SHR-control group were given a normal diet and the SHR-vitamin C group a diet supplemented with vitamin C (1000 mg/kg feed) for the next 9 weeks. After nine weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared to WKY controls and the SHR-vitamin C group. SHR-controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin C supplementation in SHRs lowered the systolic blood pressure, tissue aldehyde conjugates and attenuated adverse renal vascular changes.

Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats.

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels, increasing cytosolic free calcium and blood pressure. N-acetyl cysteine normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. It is known that dietary vitamin B6 supplementation can increase the level of endogenous cysteine. Our objective was to investigate whether a dietary supplementation of vitamin B6 can prevent hypertension and associated changes in SHRs. Starting at 7 weeks of age, animals were divided into three groups of six animals each. Animals in WKY-control group and SHR-control group were given a normal vitamin B6 diet; and SHR-vitamin B6 group, a high vitamin B6 diet (20 times the recommended dietary intake; RDA) for the next 14 weeks. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls compared to WKY controls. These animals also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation attenuated the increase in systolic blood pressure, tissue aldehyde conjugates and associated changes. These results further support the hypothesis that aldehydes are involved in increased systolic blood pressure in SHRs and suggest that vitamin B6 supplementation may be an effective antihypertensive.

Antihypertensive effect of low ethanol intake in spontaneously hypertensive rats

Light to moderate drinking in humans lowers the risk of coronary heart disease and may lower blood pressure. We examined the effect of chronic low daily alcohol consumption on blood pressure, platelet cytosolic free calcium [Ca2+]i, tissue aldehyde conjugates and renal vascular changes in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). We also examined the effects of the same weekly amount of alcohol consumption over a one day period each week simulating weekend drinking in humans. Animals, age 7 weeks, were divided into six groups of six animals each and were treated as follows: WKY and SHR control, normal drinking water; WKY and SHR, 0.5% ethanol in drinking water; WKY and SHR, 3.5% ethanol in drinking water one day/week. After 14 weeks systolic blood pressure, platelet [Ca2+]i, liver, kidney and aortic aldehyde conjugates were significantly higher (p < 0.05) in untreated SHRs as compared to untreated WKYs. Daily 0.5% ethanol consumption in SHRs significantly (p < 0.05) attenuated these changes and also attenuated smooth muscle cell hyperplasia and narrowing of the lumen in small arteries and arterioles of the kidney. WKY rats treated with 0.5% ethanol had lower aldehyde conjugates without any significant effect on blood pressure and platelet [Ca2+]i as compared to WKY controls. Consumption of 3.5% ethanol one day/week did not affect blood pressure and associated changes in normotensive WKY rats or hypertensive SHRs as compared to their respective controls. These results suggest that chronic daily low ethanol intake lowers blood pressure in SHRs by lowering tissue aldehyde conjugates and cytosolic free calcium.

Ethanol-Induced Hypertension: The Role of Acetaldehyde

Within the hypertensive population, as many as 30% may have alcohol-induced hypertension [1]. Increased prevalence of hypertension in heavy drinkers was first described by Lian in 1915 [2], and over the past 20 years, epidemiological and clinical studies have confirmed this association [3–6]. Recently, using animal models, the biochemical mechanisms whereby ethanol intake leads to hypertension are beginning to be understood [7–15].

A comparison between haemodynamic effects of vasopressin analogues

Some analogues of arginine vasopressin (AVP) reportedly possess hypotensive properties, and two such peptides are Cys1-Tyr2-Phe3-Val4-Asn5-Cys6-Pro7-d-Arg8-Gly9-NH2 (VD-AVP) and d(CH2)5-Cys1-d-Tyr(Et)2-Arg3-Val4-Asn5-Cys6-Lys7-Lys8-ethylenediamine9 (TA-LVP). In the present investigation we examined the effects of TA-LVP (0.3, 1.0 and 3.0 μg/kg/min), VD-AVP (0.3, 1.0 and 3.0 μg/kg/min) and AVP (1.0, 3.0, 10 ng/kg/min) on haemodynamics, blood volume (BV) and plasma troponin levels in anaesthetised rats. Infusion of TA-LVP significantly (P<0.05) reduced blood pressure (−45±3%; n=8; mean ± SEM), mean circulatory filling pressure (Pmcf; −41±3%), and cardiac output (CO; −59±4%). The reduction in CO at a lower dose of TA-LVP was due to reduced venous tone, while at higher doses the reduction was predominantly the result of reduced BV (−35±4%). The large decrease in BV during the infusion of TA-LVP, substantially increased resistance to venous return (50±11%), which was the main contributor in reducing CO. Administration of AVP significantly increased blood pressure (41±4%) and arterial resistance (98±16%) without any impact on Pmcf and BV, while significantly reducing CO (−26±5%). Infusion of VD-AVP did not produce hypotension, but produced a modest but significant reduction in CO (−18±5%) and insignificant but moderate increases in peripheral resistance (30±12%) and resistance to venous return (28±8%). Plasma troponin levels were not affected by any of the peptides. The hypotensive action of TA-LVP was due to a reduction in CO as a result of a reduced pre-load, while the pressor effect of AVP increased after-load sufficiently to impede flow, reducing CO. VD-AVP was devoid of any hypotensive effects, suggesting that V2-vasopressin receptors are most likely to play a limited role in the control of cardiac and vascular function in these animals.

Influence of tangential stress on mechanical responses to vasoactive agents in human saphenous vein with and without perivascular adipose tissue

AIM Improvement in short-term patency of vein grafts harvested with the surrounding tissue and no distention has been noted. The influence of transient tangential stress on mechanical function to vasoactive agents in isolated human saphenous veins stripped or with attached perivascular adipose tissue was assessed. METHODS Concentration-response curves to noradrenaline, 5-hydroxytryptamine, methylcholine, sodium nitroprusside and nicardipine were constructed for veins exposed to no, low (approximately 120 mmHg) or high (approximately 240 mmHg) tangential stress. RESULTS Tangential stress did not affect contractile effects of noradrenaline or relaxant effects of methylcholine and sodium nitroprusside. Regression analysis of the concentration-response curve to 5-hydroxytryptamine revealed a significant (P=0.042) increase in sensitivity in saphenous veins without perivascular adipose tissue exposed to no tangential stress, compared with veins with attached adipose tissue. Exposure to high stress significantly (P=0.024) increased the potency of 5-hydroxytryptamine in blood vessels without perivascular adipose tissue, as opposed to veins with adipose tissue. Relaxant responses to nicardipine in veins with perivascular adipose tissue were significantly (P=0.001) affected by exposure to low tangential stress compared with no or high tangential stress. A parallel comparison revealed that intact veins compared with those without perivascular adipose tissue exposed to low stress were significantly (P=0.020) more resistant to the relaxant effects of nicardipine. CONCLUSION The findings of the present report support the view that tangential stress has an impact on the actions of vasoactive agents, but this influence is variable and factor(s) released from perivascular adipose tissue may have a bearing on the observed effect.

A Nutritional Approach to Prevent High Blood Pressure

In essential hypertension, excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. Abnormalities in carbohydrate metabolism may underlie the etiology of the clinical course of hypertension. Insulin resistance and glucose intolerance is a common feature of hypertension in humans and in animal models. Elevated endogenous aldehydes in spontaneously hypertensive rats may be due to increased production of reactive aldehydes such as methylglyoxal, when the glycolytic pathway of glucose metabolism is impaired. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure by binding excess endogenous aldehydes and normalizing Ca2+ channels and cytosolic free calcium. Dietary sup-plementation with nutrients which can increase endogenous cysteine and glutathone may improve carbohydrate metabolism, lower blood pressure and normalize associated biochemi-cal and histopathological changes. This nutritional approach to lower blood pressure has been demonstrated in spontaneously hypertensive rats, a model of human essential hypertension using supplementation with either vitamin B6, vitamin C, N-acetyl cysteine or lipoic acid.

Alteration in hemodynamic effects of interleukin 2 after treatment with indomethacin in anesthetized rats.

The cardiovascular effects of interleukin 2 (IL2), were investigated in animals pretreated with indomethacin. Bolus intravenous administration of IL2 alone caused a significant reduction in cardiac output over time. Pretreatment with indomethacin significantly accentuated the reduction in cardiac output produced by IL2. The administration of IL2 or indomethacin alone or combined had no significant effects on dP/dt, heart rate or plasma troponin levels. As well, administration of either compound alone or combined had limited effects on mean circulatory filling pressure and arterial blood pressure. Injection of IL2 alone significantly increased resistance to venous return and arterial resistance at 3h post injections. Pretreatment with indomethacin caused IL2 to produce a significantly greater increase in arterial resistance and resistance to venous return. Administration of IL2 and indomethacin combined also produced significant reduction in stroke volume than IL2 or indomethacin alone. The injection of IL2 or indomethacin alone or combined had no significant impact on blood volume. Acute administration of IL2 appears to have no negative inotropic or chronotropic effects and its impact in reducing cardiac output is the result of an increase in vascular resistance. It seems that activation of prostanoids, possibly prostacyclin, has an acute beneficial effect in attenuating the initial negative effects of IL2 on cardiac output.