Antihypertensive effect of α- and β-adrenergic blockade in obese and lean hypertensive subjects

Wofford, Marion R.; Anderson, Douglas C.; Brown, C. Andrew; Jones, Daniel W.; Miller, Margaret E; Hall, John E.

doi:10.1016/s0895-7061(01)01293-6

Cited by 172 publications

(135 citation statements)

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“…22 These results confirm the importance of SNS activity in BP regulation and suggest that an increased SNS activity as a mediator for the relation between obesity and hypertension can differ between different ethnic groups. 21 Wofford et al 23 showed that BP Gender differences in ABPM A Kagan et al is more sensitive to adrenergic blockade in obese than in lean hypertensive patients. These findings suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity.…”

Section: Discussionmentioning

confidence: 99%

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

Kagan

Faibel²,

Ben-Arie

et al. 2006

J Hum Hypertens

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The incidence of obesity has increased enormously in the past several decades, and has been described as a modern epidemic. Obesity is a major factor contributing to hypertension. To the best of our knowledge, no study of ambulatory blood pressure monitoring (ABPM) comparing men with women in relation to body mass indexes (BMI) has been performed. From December 2002 to May 2006, we performed 24-h ABPM in 5950 subjects (3102 men and 2848 women), with a wide range of BMI (range 15.9-53.2 kg/m 2 ). We defined obese subjects as those with BMIX30.0 kg/m 2 , overweight subjects as those with BMI425.0 and o30.0 kg/m 2 , and normal subjects as those with BMIp25.0 kg/m 2 . Data on 989 subjects (501 men and 488 women) aged from X18 to p69 years without antihypertensive treatment, atrial fibrillation or diabetes were included for analysis. We consistently found that obese men had the expected increased heart rate compared to normal and overweight men, whereas women (normal, overweight and obese) had similar HRs. In addition, normal and obese women had similar diastolic blood pressures (BP), as opposed to obese men, who had raised diastolic BP. These results may indicate that different pathogenetic mechanisms may be involved in the relationship between obesity and hypertension in men and women.

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Section: Discussionmentioning

confidence: 99%

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

Kagan

Faibel²,

Ben-Arie

et al. 2006

J Hum Hypertens

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“…Combined a-and b-adrenergic blockade significantly reduced BP in obese compared with lean patients with essential hypertension. 9 However, elevated sympathetic activity did not seem to account for the increased heart rate in obesity. Instead, the elevated heart rate seems to be the effect of decreased parasympathetic activity.…”

Section: Sympathetic Activation In Obesitymentioning

confidence: 97%

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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“…Also, plasma norepinephrine is increased in obese normotensive and hypertensive subjects [Julius et al, 2000;Grassi et al, 1998 (b)]. In addition, reduction in arterial pressure with systemic sympathetic inhibition with α-and β-adrenergic and ganglion blockers is more pronounced in obese than in lean subjects [Wofford et al, 2001;Paranjape et al, 2007]. These observations strongly suggest that increased sympathetic nerve activity elevates arterial pressure in obesity.…”

Section: General Considerationsmentioning

confidence: 97%

“…Some lines of evidence support this prevailing concept. For instance, arterial pressure has been shown to be more sensitive to the hypotensive effect of dual α-and β-adrenergic blockade or systemic ganglion blockade in obese versus lean subjects, suggesting an important role of the sympathetic nervous system on the regulation of arterial pressure in obesity [Wofford et al, 2001;Shibao et al, 2007].…”

Section: Sympathetic Regulation Of Vascular Function In Obesitymentioning

confidence: 99%

“…Sympathoactivation has been demonstrated in human obesity by plasma norepinephrine measurements, 24-hour urinary cathecolamine excretion, measurements of radiolabeled norepinephrine spillover, microneurographic measurement of mSNA, dual α-and β-adrenergic inhibition, and systemic ganglion blockade [Troisi et al, 1991;Scherrer et al, 1994;Grassi et al, 1995;Eikelis et al, 2003;Wofford et al, 2001;Shibao et al, 2007]. Furthermore, body fat content is positively correlated with mSNA and arterial pressure [Jones et al, 1996;Wilson et al, 2002] whereas reductions in body weight from a hypocaloric diet decrease mSNA, plasma norepinephrine and arterial pressure [Grassi et al, 1998 (b);Lecheminant et al, 2007].…”

Section: Hypertension Introductionmentioning

confidence: 99%

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Sympathetic Vascular Tone in Human Obesity

Agapitov

Sinkey

Dopp

et al. 2004

Journal of Hypertension

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Obesity is associated with increased sympathoactivation that elevates arterial pressure. However, the mechanism linking sympathetic activation to arterial pressure is unclear. Specifically, it has never been demonstrated unequivocally that sympathetically mediated vasoconstriction is increased in obesity. This project tested the hypothesis that sympathetic vascular tone is increased in obese normotensive and hypertensive subjects.The effect of weight loss on sympathetic vascular tone was also assessed.Sympathetic vascular tone was assessed as forearm vasodilatation to intra-arterial phentolamine (α 1/2 -adrenergic receptor antagonist). Pharmacological responses were correlated with skeletal muscle sympathetic nerve activity (mSNA). Obese subjects with and without hypertension had increased mSNA. However, the vasodilatator response to phentolamine was not augmented in obese normotensive and hypertensive subjects versus lean controls. Additionally, weight loss did not alter phentolamine's vasodilatator response, despite reducing mSNA and arterial pressure in obese groups. These results indicate that sympathetic vascular tone is not increased in obesity despite higher mSNA.These studies also assessed forearm resistance vessel function using intra-arterial nitroprusside (nitric oxide donor) and isoproterenol (β 2 -adrenergic receptor agonist). The effects of weight loss on these responses were studied in the obese groups. The response to both vasodilators was blunted, but only in obese hypertensive subjects. Weight loss normalized the response to nitroprusside but not to isoproterenol. This result suggests that obesity-related hypertension is associated with vascular smooth muscle dysfunction, which can be improved by weight loss. Blunted vasodilatation to isoproterenol suggests an abnormality on β 2 -adrenergic receptor-dependent mechanisms that may or may not depend on the endothelium. Also, mental stress-induced forearm vasodilatation was blunted in obese normotensive subjects, which was not normalized by weight loss. 2In conclusion, increased sympathetic nerve activity does not augment forearm sympathetic vascular tone. This dissociation could be due to opposing local factors (e.g. insulin, leptin) or to a different target of limb sympathoactivation (e.g. adipocytes vs. vascular). Sympathetic drive to tissues other than the peripheral circulation may play a more important role in arterial pressure elevation in obesity, either directly or indirectly.Abstract Approved: ____________________________________ Thesis Supervisor ____________________________________

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Antihypertensive effect of α- and β-adrenergic blockade in obese and lean hypertensive subjects

Cited by 172 publications

References 21 publications

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

Gender differences in ambulatory blood pressure monitoring profile in obese, overweight and normal subjects

Mechanisms of obesity-induced hypertension

Sympathetic Vascular Tone in Human Obesity

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