Glucocorticoid‐Induced Hypertension: From Mouse To Man

Whitworth, Judith A.; Schyvens, Christopher G.; Zhang, Yi; Mangos, George; Kelly, John J.

doi:10.1046/j.1440-1681.2001.03584.x

Cited by 62 publications

(37 citation statements)

References 33 publications

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“…However, a similar independent role for ACTH in high concentrations has also been proposed (Whitworth et al 2001). In the present study, we clearly show that AVP alone is capable of exerting equivalent cardiopressor responses to combined CRH and AVP, indicating that it is AVP rather than the combination of AVP and high ACTH produced after the CRH and AVP bolus, which is responsible for the cardiovascular responses observed in the present study.…”

Section: Discussionsupporting

confidence: 88%

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Gardner¹,

Bon²,

Dandrea

et al. 2006

Journal of Endocrinology

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Glucocorticoids are proposed to act as intermediary factors that transcribe the developmental programming sequelae of maternal nutrient restriction (NR). Periconceptional undernutrition of sheep markedly activates fetal hypothalamicpituitary-adrenal (HPA) axis activity leading to preterm birth, while transient undernutrition during late gestation in sheep programs adult HPA axis function. To date, no study has examined resting or stimulated HPA axis function in young adult offspring following a periconceptional nutritional challenge. In the present study, 20 ewes were either periconceptionally undernourished (50% metabolisable energy requirements from days 1 to 30 gestation; NR, nZ8) or fed to control levels (100% requirement; controls, nZ12) to term (147 days gestation). Ewes were blood sampled remotely at 2 and 30 days using automated blood sampling equipment. Thereafter, offspring (controls, nZ6/6 males/females; NR, nZ4/4 males/females) were reared to 1 year of age and on separate days received either an i.v. corticotrophin-releasing hormone (CRH; 0$5 mg/kg) and vasopressin (AVP; 0$1 mg/kg) challenge or a synthetic ACTH i.v. bolus (Synacthen; 1$25 mg/kg), and blood samples were taken (manually and remotely) at appropriate intervals for measurement of plasma ACTH and cortisol accordingly. Resting plasma cortisol, assessed remotely, was similar in ewes during undernutrition (control 18$3G1$4 vs NR 23$4G1$9 nmol/l) and in offspring at 4 months of age (control male 17$6G2$9; control female 17$2G0$4, NR male 16$5G3$1, NR female 21$7G4$0 nmol/l). At 12 months of age, however, resting plasma cortisol was significantly increased in NR females (control male 28$0G1$5, control female 32$9G9, NR male 32G7, NR female 53G10 nmol/l, F 5$7, PZ0$02) despite no difference in plasma ACTH concentration. There was an interaction between nutritional group and gender for both the pituitary and adrenal responses to CRH and AVP, i.e. for controls, females exhibited increased plasma ACTH or cortisol relative to males but for NR this trend was either not present or reversed. The adrenocortical response to synthetic ACTH was gender-dependent only, being greater in female offspring. Combined CRH and AVP provoked a transient hypertension and marked bradycardia in all animals, irrespective of dietary group or gender and could be effectively reproduced by an AVP bolus alone. In conclusion, the present study has shown that periconceptional undernutrition of sheep has only a minor influence on HPA axis function in their young adult offspring when considered alongside the effect of gender per se.

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Section: Discussionsupporting

confidence: 88%

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Gardner¹,

Bon²,

Dandrea

et al. 2006

Journal of Endocrinology

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“…Glucocorticoids increase food intake, reduce energy expenditure and they promote insulin resistance, fat accumulation 68 and hypertension. 69,70 Many rodent models of obesity, which are characterized by hypercorticosteronemia with weight gain, displayed body weight normalization after adrenalectomy and reinstated by glucocorticoid replacement. Although plasma glucocorticoid levels are normal in human idiopathic obesity, 71 it has been proposed that intra-adipose glucocorticoid action is increased.…”

Section: Corticosteroidsmentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies. Hypertension Research (2010) 33, 386-393; doi:10.1038/hr.2010.9Keywords: leptin; obesity; pressure natriuresis; rennin-angiotensin-aldosterone system; sympathetic nervous system INTRODUCTION Obesity is a common disorder that develops from the interaction between the genotype and the environment and involves social, behavioral, cultural, physiological, metabolic and genetic factors. A large number of studies have shown that obesity has an important negative impact on health in a population, leading to the recommendation for general practitioners to have an important function in the management of this condition and of its associated comorbidities such as hypertension, hyperlipidemia and hyperinsulinemia/insulin resistance. The relationship between obesity and hypertension is well established both in adults and children. 1,2 Obese individuals exhibit higher levels of office as well as ambulatory blood pressure (BP) from childhood to old age. Obese subjects display higher BP levels than non-obese individuals even in the normotensive range. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the probability of adverse cardiovascular outcomes, and raises considerations for aggressive treatment strategies. 3 The mechanisms through which obesity directly causes hypertension are still an area of research. Human and animal studies have elucidated the function of adipose tissue derivatives (adipokines and cytokines), neurohumoral pathways, metabolic functions and modulation of pressor/depressor mechanisms. Although obesity-related hypertension may be the result of a combinatio...

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“…However, in the adult rat, the pressor effects of ACTH are not ameliorated by endothelin-1 antagonism with bosetan (52). Unlike the actions of mineralocorticoids, glucocorticoid-induced hypertension is not mediated by increased sympathetic tone (53) and in humans is associated with either normal or decreased sympathetic activity (54). In keeping with evidence in humans that suppression of the nitric oxide system may play a role in cortisol-induced hypertension (55)(56)(57)(58), we have demonstrated impairment of fetal femoral artery nitric oxide production after three courses of DM administration to the ewe (59).…”

Section: Discussionmentioning

confidence: 91%

Maternally Administered Dexamethasone at 0.7 of Gestation Suppresses Maternal and Fetal Pituitary and Adrenal Responses to Hypoxemia in Sheep

et al. 2004

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Women who are at risk of preterm delivery are treated with antenatal steroids to facilitate fetal lung maturation. During this period, there is a potential for fetal or maternal hypoxemia to occur. Fetal responses to hypoxemia in sheep are well documented. However, less is known regarding maternal responses to hypoxemia. Therefore, we determined the effects of dexamethasone (DM) on maternal and fetal responses to hypoxemia in sheep. Ewes received four i.m. injections of DM or saline at 12-h intervals beginning at 103 d of gestation. Samples for ACTH, cortisol, and glucose were collected at 0900 h. At 105 d of gestation, hypoxemia was induced for 1 h by maternal nitrogen gas inhalation. Samples for ACTH, cortisol, and glucose were collected at 15-min intervals before, during, and after the hypoxemia challenge. Fluorescent microspheres were administered to the mother and the fetus before and during hypoxemia to measure organ perfusion. DM suppressed basal fetal and maternal cortisol and ACTH concentrations but increased glucose levels. DM also increased fetal but not maternal blood pressure. In control subjects, hypoxemia elevated fetal and maternal cortisol and ACTH concentrations. These responses were obliterated by DM. Hypoxemia increased blood pressure in DM-exposed fetuses but not in control subjects. In addition, hypoxemia decreased fetal adrenal vascular resistance in saline but not DM fetuses or ewes from either treatment group. In summary, maternal administration of a low dose of DM at 0.7 of gestation suppresses maternal and fetal adrenal function and changes fetal responses to hypoxemic stress to resemble those observed later in gestation. Administration of synthetic glucocorticoids, such as betamethasone and dexamethasone (DM), to accelerate fetal lung maturation has become a routine treatment for women who are at risk of preterm labor (1, 2). This treatment is designed to elevate fetal plasma glucocorticoid levels, mimicking the maturational effects that normally occur close to term in humans and other species produced by the endogenous prepartum increases in fetal plasma cortisol (3-6). Prophylactic antenatal glucocorticoid treatment has resulted in a significant decrease in preterm infant morbidity and mortality (1,(7)(8)(9)(10)(11)(12).Despite the clear benefits of antenatal maternal glucocorticoid therapy, unwanted effects on organ systems other than the lung have been identified in both clinical human and research animal studies. For instance, exogenous glucocorticoid use has been associated with reduced weight and head circumference in infants at birth (7,13,14). In addition to the effects on fetal growth, antenatal glucocorticoid treatment administered to fetal sheep in the last third of gestation increases fetal blood pressure (BP) (15)(16)(17)(18)(19). Repeated maternal betamethasone administration in sheep also suppresses neuroendocrine and adrenal responsiveness in the preterm newborn lamb (20,21).Responses to acute hypoxemia in fetal sheep Ͼ120 d of gestation (dGA) are well established (22...

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Glucocorticoid‐Induced Hypertension: From Mouse To Man

Cited by 62 publications

References 33 publications

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Effect of periconceptional undernutrition and gender on hypothalamic–pituitary–adrenal axis function in young adult sheep

Mechanisms of obesity-induced hypertension

Maternally Administered Dexamethasone at 0.7 of Gestation Suppresses Maternal and Fetal Pituitary and Adrenal Responses to Hypoxemia in Sheep

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