The effect of alpha-lipoic acid on mitochondrial superoxide and glucocorticoid-induced hypertension.

Aims: To examine the effect of alpha-lipoic acid, an antioxidant with mitochondrial superoxide inhibitory properties, on adrenocorticotrophic hormone- (ACTH-HT) and dexamethasone-induced hypertensions (DEX-HT) in rats and if any antihypertensive effect is mediated via mitochondrial superoxide inhibition.

Methods: In a prevention study, rats received ground food or alpha-lipoic-acid-laced food (10 mg/rat/day) for 15 nights. Saline, adrenocorticotrophic hormone (ACTH, 0.

Glucocorticoid-induced hypertension and the nitric oxide system.

Glucocorticoid hormones, both naturally occurring and synthetic, have long been recognized as a major cause of hypertension. There are well-described experimental models of glucocorticoid-induced hypertension, such as adrenocorticotropic hormone- and dexamethasone-induced hypertension in rats, although the exact mechanism of glucocorticoid-induced hypertension remains unclear. It was initially considered to be due to mineralocorticoid receptor activation but more recent studies have not supported this notion.

How do glucocorticoids cause hypertension: role of nitric oxide deficiency, oxidative stress, and eicosanoids.

The exact mechanism by which glucocorticoid induces hypertension is unclear. Several mechanisms have been proposed, although there is evidence against the role of sodium and water retention as well as sympathetic nerve activation. This review highlights the role of nitric oxide-redox imbalance and their interactions with arachidonic acid metabolism in glucocorticoid-induced hypertension in humans and experimental animal models.

The glucocorticoid receptor is required for experimental adrenocorticotrophic hormone-induced hypertension in mice.

1. In the present study, we have (i) measured basal blood pressure by telemetry in wild-type (WT) and glucocorticoid receptor knockout (GRKO) mice; (ii) investigated whether or not adrenocorticotrophic hormone (ACTH) can induce hypertension in GRKO mice; and (iii) investigated the effect of mineralocortocoid receptor blockade on the cardiovascular physiology of GRKO mice. 2.

Effects of sepiapterin supplementation and NOS inhibition on glucocorticoid-induced hypertension.

Background: Glucocorticoid-induced hypertension is associated with imbalance between nitric oxide (NO) and superoxide. One of the pathways that causes this imbalance is endothelial NO synthase (eNOS) uncoupling. In the present study, adrenocorticotrophic hormone (ACTH)- and dexamethasone-treated rats were further treated with sepiapterin, a precursor of tetrahydrobiopterin, or N-nitro-L-arginine (NOLA), an inhibitor of NOS, to investigate the role of eNOS uncoupling in glucocorticoid-induced hypertension.

Economic hardship associated with managing chronic illness: a qualitative inquiry.

Background: Chronic illness and disability can have damaging, even catastrophic, socioeconomic effects on individuals and their households. We examined the experiences of people affected by chronic heart failure, complicated diabetes and chronic obstructive pulmonary disease to inform patient centred policy development. This paper provides a first level, qualitative understanding of the economic impact of chronic illness.

Hemodynamics of dexamethasone-induced hypertension in the rat.

Although dexamethasone (DEX) is known to cause hypertension in humans and in animals, the hemodynamic characteristics of DEX-induced hypertension (DEX-HT) in the rat remain unclear. This study evaluated central and regional hemodynamics, and the role of total peripheral resistance (TPR) using a vasodilator minoxidil. Rats were divided into four groups, namely saline (n=20), DEX (n=21), minoxidil+saline (n=10) and minoxidil+DEX (n=10).

The role of 20-hydroxyeicosatetraenoic acid in adrenocorticotrophic hormone and dexamethasone-induced hypertension.

Objective: 20-hydroxyeicosatetraenoic acid (20-HETE) is a potent constrictor in small arteries and also has natriuretic properties. Urinary 20-HETE excretion is increased in adrenocorticotrophic hormone (ACTH)-induced hypertensive rats. In the present study, we investigated the effect of a specific enzyme inhibitor of 20-HETE production, N-hydroxy-N'-(4-butyl-2-methylphenyl) formamidine (HET0016), on glucocorticoid-induced hypertension in rats, a sodium-independent model.

N-Acetylcysteine prevents but does not reverse dexamethasone-induced hypertension.

1. We have shown previously that N-acetylcysteine (NAC) prevents the increase in blood pressure induced by adrenocorticotropin treatment. The present study investigated the effect of NAC on dexamethasone (Dex)-induced hypertension.

Reactive oxygen species and glucocorticoid-induced hypertension.

1. There is increasing evidence for a role of oxidative stress and nitric oxide deficiency in experimental glucocorticoid-induced hypertension, as evidenced by increased biomarkers of oxidative stress; the effectiveness of antioxidants or reduced NADPH oxidase antagonists in lowering blood pressure; and secondary upregulation of endogenous antioxidant enzymes in response to oxidative stress. 2.

Arachidonic acid metabolism in glucocorticoid-induced hypertension.

1. Products of metabolism of arachidonic acid, such as 20-hydroxyeicosatetraenoic acid (20-HETE), thromboxane A(2) (TXA(2)) and prostaglandin I(2) (PGI(2)), regulate vascular tone. Among them, 20-HETE is a potent constrictor in small arteries that also has natriuretic properties.

Antioxidant vitamins and adrenocorticotrophic hormone-induced hypertension in rats.

This study examined whether the anti-oxidants ascorbic acid, alpha- or gamma-tocopherol, could modify adrenocorticotrophic hormone (ACTH)-hypertension in Sprague-Dawley rats, a model associated with increased oxidative stress. Systolic blood pressure (SBP) was measured by the tail-cuff method. After four days of ascorbic acid (AA) (200 mg/kg/day drinking) or alpha-tocopherol (500 mg/kg/d i.

Aspirin prevents and partially reverses adrenocorticotropic hormone-induced hypertension in the rat.

Background: Glucocorticoid-induced hypertension is associated with increased oxidative stress. The aim of the present study was to investigate the effects of aspirin, a potent antioxidant, on adrenocorticotropic hormone (ACTH) and dexamethasone (Dex)-induced hypertension.

Methods: Male Sprague-Dawley (SD) rats were treated with saline, ACTH (0.

Should eponyms be abandoned? No.

Medicine has been enthusiastic in naming tests, symptoms, and diseases after their discovers. and argue that eponyms are no longer appropriate, but believes they remain a useful reflection of medical history

Assessing outcomes of health and medical research: do we measure what counts or count what we can measure?

Governments world wide are increasingly demanding outcome measures to evaluate research investment. Health and medical research outputs can be considered as gains in knowledge, wealth and health. Measurement of the impacts of research on health are difficult, particularly within the time frames of granting bodies.

Role of xanthine oxidase in dexamethasone-induced hypertension in rats.

1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2.

Folic acid prevents and partially reverses glucocorticoid-induced hypertension in the rat.

Background: To investigate the effect of folic acid on the increased pressure in rats treated with either adrenocorticotropic hormone (ACTH) or dexamethasone (Dex), and to further investigate the role of tetrahydrobiopterin (BH(4)) in any effect of folic acid by comparing the effect of BH(4) with that of folic acid in Dex hypertension.

Methods: Male Sprague-Dawley (SD) rats were treated with saline, subcutaneous ACTH (0.2 mg/kg/d) or Dex (10 microg/rat/d).

Blood pressure and control of cardiovascular risk.

Two key early 20th century notions, the first the primacy of diastolic pressure in determining risk, and the second that hypertension is a discrete disorder, have proved to be incorrect. We now recognize the primacy of systolic pressure as a risk factor for cardiovascular disease and that hypertension is an arbitrary definition. In the early 21st century, we are moving away from a dichotomous approach to risk classification, and away from notions of hypertension and normotension towards an appreciation that blood pressure-related risk is continuous.

Cardiovascular consequences of cortisol excess.

Cushing's syndrome is a consequence of primary or, more commonly, secondary oversecretion of cortisol. Cardiovascular disease is the major cause of morbidity and mortality in Cushing's syndrome, and excess risk remains even in effectively treated patients. The cardiovascular consequences of cortisol excess are protean and include, inter alia, elevation of blood pressure, truncal obesity, hyperinsulinemia, hyperglycemia, insulin resistance, and dyslipidemia.

Effect of synthetic corticosteroids on vascular reactivity in the human forearm.

Exogenous cortisol raises blood pressure (BP) and suppresses acetylcholine (ACh)-induced vasodilatation in healthy male volunteers. This study tests the hypothesis that the activation of either classical type I or II corticosteroid receptors by synthetic corticosteroids induces endothelial dysfunction. In two separate studies, dexamethasone or fludrocortisone was administered to healthy male subjects over five days.

Best practices in use of research evidence to inform health decisions.

The WHO Advisory Committee on Health Research (ACHR) is committed to the notion that WHO should exemplify best practice in use of research evidence to inform decisions about health. A major ongoing initiative of the ACHR is the Sub-committee on the Use of Research Evidence (SURE). This group is examining WHOs roles and responsibilities in the use of health research to inform decisions about health.

Species variability in cardiovascular research: the example of adrenocorticotrophin-induced hypertension.

1. Lawrie Beilin has contributed greatly to international hypertension research through both animal and human studies. 2.