Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives

Grassı, Guıdo; Dell’Oro, Raffaella; Facchini, A.; Trevano, Fosca Quarti; Bolla, G.; Mancia, Giuseppe

doi:10.1097/00004872-200412000-00019

Cited by 292 publications

(241 citation statements)

References 30 publications

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“…This is shown in Fig. 3, which displays the results of a recent microneurographic study in which the muscle sympathetic neural drive was assessed in abdominal as well as in peripheral obesity (20). The results clearly indicate that the degree of sympathetic activation (and the magnitude of the insulin resistance state) is much greater in patients with visceral body fat deposits than in those with peripheral distribution of the adipose tissue.…”

Section: Sympathetic Function In Hypertension and In Obesitymentioning

confidence: 75%

“…This is based on the evidence that 1) cardiovascular as well as metabolic function are modulated by sympathetic mechanisms and 2) several of the pathologic states clustering in the metabolic syndrome already display an increased adrenergic drive (2,3,10,(18)(19)(20). This is also based on the finding that when obesity and hypertension are concomitantly present in the same patient, the degree of sympathetic activation is much greater than in patients with either condition singly (24).…”

Section: Sympathetic Overdrive In the Metabolic Syndromementioning

confidence: 99%

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Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Grassı

2006

Hypertens Res

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121

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Section: Sympathetic Function In Hypertension and In Obesitymentioning

confidence: 75%

Section: Sympathetic Overdrive In the Metabolic Syndromementioning

confidence: 99%

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Grassı

2006

Hypertens Res

Self Cite

121

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“…It has been known for over two decades that insulin stimulates sympathetic activity [4] and, more recently, that this stimulation occurs at levels of insulin that are well within the physiological range [5]. For the last 15 years it has been known that obese humans have increased sympathetic activity [6], and Grassi and colleagues recently demonstrated that sympathetic activation is greater in subjects with the central, as opposed to the peripheral, form of obesity [7]. It is a reasonable inference, therefore, that insulin stimulates the sympathetic nervous system in obese individuals and that insulin-mediated sympathetic stimulation exerts a pro-hypertensive effect in this group.…”

mentioning

confidence: 99%

Insulin resistance and the metabolic syndrome

Landsberg

2005

Diabetologia

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In this issue of Diabetologia, Grassi and colleagues report increased muscle sympathetic nerve activity in patients with a collection of cardiovascular risk factors known as the metabolic syndrome [1]. They present evidence that the increase in sympathetic activity in this syndrome is related to insulin resistance and is associated with decreased baroreflex sensitivity.Why is this important? Because the metabolic syndrome is associated with significant cardiovascular risk, and understanding the pathogenesis of this constellation of factors can help define therapeutic strategies to reverse or mitigate the risk. There are four critical features of the metabolic syndrome: (1) obesity, particularly the central or abdominal form of obesity; (2) insulin resistance and hyperinsulinaemia; (3) hypertension; and (4) a characteristic dyslipidaemia consisting of high triglycerides and low HDL cholesterol [2]. Moreover, these abnormalities are associated; they occur together with increased frequency, as demonstrated in population studies. Additional risk factors that may be associated with the syndrome include type 2 diabetes, hyperuricaemia, microalbuminuria and coagulation abnormalities that constitute a pro-thrombotic diathesis. The clinician can readily diagnose the metabolic syndrome using the well-established criteria that were applied in the study of Grassi et al.[1] to identify appropriate subjects. These criteria use waist circumference as a reasonable surrogate for the abdominal form of obesity. The current worldwide epidemic of obesity highlights the importance of this syndrome.What are the threads that tie the seemingly diverse manifestations of this syndrome together? The defining features of obesity and insulin resistance are relatively well-understood and, together, can rationally and convincingly explain the hypertension and dyslipidaemia [3]. For the last 100 years, hypertension has been known to be closely associated with obesity. It has been known for four decades that obesity and type 2 diabetes are associated with hyperinsulinaemia; the latter reflects enhanced pancreatic beta cell secretion in the face of an impairment of muscle glucose uptake, the defining abnormality of insulin resistance. When the pancreatic beta cell reserve falters, IGT or overt type 2 diabetes develops. It has been known for over two decades that insulin stimulates sympathetic activity [4] and, more recently, that this stimulation occurs at levels of insulin that are well within the physiological range [5]. For the last 15 years it has been known that obese humans have increased sympathetic activity [6], and Grassi and colleagues recently demonstrated that sympathetic activation is greater in subjects with the central, as opposed to the peripheral, form of obesity [7]. It is a reasonable inference, therefore, that insulin stimulates the sympathetic nervous system in obese individuals and that insulin-mediated sympathetic stimulation exerts a pro-hypertensive effect in this group. This inference is strengthened by the correlation o...

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“…The differences between these two studies might be attributed to the greater number of men with visceral obesity in Grassi's study [Jones et al, 1996;Grassi et al, 2005] because central obesity increases mSNA more markedly than peripheral obesity Grassi et al, 2004].…”

Section: Sympathetic Activation Associated With Obesitymentioning

confidence: 93%

“…Third, central obesity and obesity-related hypertension attenuate the inhibitory action of baroreflex on sympathetic outflow [Grassi et al, 2000;Beske et al, 2002;Grassi et al, 2004]. Conversely, weight loss improves baroreflex function [Alvarez et al, 2005].…”

Section: Sympathetic Activation Associated With Obesitymentioning

confidence: 99%

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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Effect of central and peripheral body fat distribution on sympathetic and baroreflex function in obese normotensives

Abstract: These data suggest that CO is characterized by a sympathetic activation greater for magnitude than that detectable in PO. This appears not to be related to gender or to baroreflex mechanisms but rather to metabolic factors, i.e. to the greater insulin resistance characterizing CO.

Cited by 292 publications

References 30 publications

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome

Insulin resistance and the metabolic syndrome

Sympathetic Vascular Tone in Human Obesity

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