This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weyer, C. Articles by Tataranni, P. A. Search for Related Content PubMed PubMed Citation Articles by Weyer, C. Articles by Tataranni, P. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Obesity Related Collections Obesity Cerebrovascular disease/stroke Risk Factors Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2000;36:531.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Ethnic Differences in Insulinemia and Sympathetic Tone as Links Between Obesity and Blood Pressure

Christian Weyer; Richard E. Pratley; Soren Snitker; Maximilian Spraul; Eric Ravussin; P. Antonio Tataranni

From the Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Ariz (C.W., R.E.P., E.R., P.A.T.); the Division of Endocrinology, Diabetes, and Nutrition, University of Maryland School of Medicine, Baltimore, Md (S.S.); and the Department of Metabolic Diseases and Nutrition, Heinrich Heine University, Düsseldorf, Germany (M.S.).

Correspondence to Christian Weyer, MD, Clinical Diabetes and Nutrition Section, National Institutes of Health, 4212 N 16th St, Room 5-41, Phoenix, AZ 85016. E-mail cweyer{at}phx.niddk.nih.gov

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Abstract—Hyperinsulinemia and increased sympathetic nervous system (SNS) activity are thought to be pathophysiological links between obesity and hypertension. In the present study, we examined the relation among heart rate (HR), blood pressure (BP), and percent body fat (hydrodensitometry or DEXA), fasting plasma insulin concentration, and muscle sympathetic nerve activity (MSNA, microneurography) in male, normotensive whites (n=42) and Pima Indians (n=77). Pima Indians have a high prevalence of obesity and hyperinsulinemia but a relatively low prevalence of hypertension. Compared with whites, Pima Indian men had a higher percent body fat (28% versus 21%) and higher fasting insulin concentrations (210 versus 132 pmol/L) but lower MSNA (27 versus 33 bursts/min) (all P<0.001). In both ethnic groups, HR and BP were positively related to percent body fat and MSNA, and both were significant independent determinants of HR and BP in multiple regression analyses. However, MSNA was positively related to percent body fat and the fasting insulin concentration in whites (r=0.60 and r=0.47, both P<0.01) but not in Pima Indians (r=0.15 and r=0.03, NS) (P<0.01 for ethnic differences in the slope of the regression lines). These results confirm the physiological importance of the SNS in normal BP regulation but indicate that the roles of hyperinsulinemia and increased SNS activity as mediators for the relation between obesity and hypertension can differ between different ethnic groups. The lack of an increase in SNS activity with increasing adiposity and insulinemia in Pima Indians may contribute to the low prevalence of hypertension in this population.

Key Words: adipose tissue • hyperinsulinism • autonomic nervous system • hypertension, obesity • ethnic groups

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Obesity is associated with an increased risk of cardiovascular diseases including hypertension, stroke, and coronary artery disease.¹ The pathophysiological mechanisms predisposing obese individuals to hypertension are not fully understood, but hyperinsulinemia and increased sympathetic nervous system (SNS) activity have been suggested to play a role.^{2 3 4 5 6} Almost 15 years ago, Landsberg² proposed that the hyperinsulinemia associated with obesity-related insulin resistance leads to increased SNS activity, which in turn contributes to increased blood pressure (BP) through chronotropic, vasoconstrictive, and antinatriuretic effects. Although there is both epidemiological and experimental evidence to support the links between obesity/hyperinsulinemia and increased SNS activity^{2 3 4 5 6 7 8 9 10} and between hyperinsulinemia/increased SNS activity and hypertension,^{2 3 4 5 6 11 12} some studies provide conflicting results.^{13 14 15 16} Thus, the potential role of hyperinsulinemia and increased SNS activity in the pathogenesis of obesity-related hypertension remains controversial.^{17 18}

Ethnicity may be an important factor to consider since insulinemia, SNS activity, and the propensity for obesity and hypertension all differ substantially among different populations.^{19 20 21} The Pima Indians of Arizona are interesting in this respect because they have the highest reported prevalence of obesity in the world but a relatively low prevalence of hypertension and atherosclerotic disease.^{20 22} Compared with whites, Pima Indians have, on average, a higher percentage of body fat and higher fasting plasma insulin concentrations, even after controlling for body size and the degree of insulin resistance,^{23 24} but lower SNS activity.^{19 25 26} On the basis of these findings, it appears that the interrelation between adiposity, insulinemia, SNS activity, and BP may differ between Pima Indians and whites. To further examine these relations and to revisit Landsberg’s hypothesis,² we analyzed data from a large number of normotensive Pima Indian and white men characterized for body composition, glucose tolerance, fasting plasma insulin concentration, resting heart rate (HR) and BP, and in whom postganglionic efferent sympathetic discharge rates to skeletal muscle (MSNA, muscle sympathetic nerve activity) were recorded directly by microneurography as a measure of SNS activity.

	Methods

Top Abstract Introduction Methods Results Discussion References

 
Subjects
Since 1992, Pima Indian and white subjects have been admitted to the Clinical Diabetes and Nutrition Section of the NIH in Phoenix, Arizona, for studies of SNS activity as measured by microneuro-graphy. For the present analysis, we included all male subjects from our database who had complete measurements of body composition, glucose tolerance and fasting plasma insulin concentration, resting HR and BP, and resting MSNA (42 whites, 77 Pima Indians, Table). All subjects were between 18 and 50 years of age, nondiabetic [75 g oral glucose tolerance test], normotensive [resting systolic (SBP) and diastolic (DBP) BP <140 and <90 mm Hg, respectively], nonsmokers at the time of the study, and healthy according to a physical examination and routine laboratory tests. None of the subjects had a personal history of hypertension or cardiovascular disease and none was taking any medication. All subjects were admitted to the National Institutes of Health Clinical Research Unit, where they were fed a weight-maintaining diet (50% of calories as carbohydrate, 30% as fat, and 20% as protein) and abstained from strenuous exercise for at least 3 days before testing. The study was approved by the Tribal Council of the Gila River Indian Community and by the Institutional Review Board of the National Institute of Diabetes and Digestive and Kidney Diseases, and all subjects provided written informed consent before participation.

View this table: [in this window] [in a new window]   Table 1. Physical, Metabolic, and Cardiovascular Characteristics of the Study Population

Anthropometric Measurements
Body composition was estimated by either underwater weighing with simultaneous determination of residual lung volume with helium dilution or by total-body dual-energy x-ray absorptiometry (DPX-L; Lunar Corp). A conversion equation was used to make measurements comparable between the two methods.²⁴ The waist-to-thigh ratio was assessed as an index of body fat distribution.

Oral Glucose Tolerance Test
After a 12-hour overnight fast, subjects underwent a 75-g oral glucose tolerance test. Plasma glucose and insulin concentrations were determined by the glucose oxidase method (Beckman Instruments) and radioimmunoassay, respectively.²⁴

Measurement of Resting MSNA, HR, and BP
On a separate day after a 12-hour overnight fast, resting MSNA was measured by microneurography as previously described.¹⁹ In brief, a tungsten microelectrode was inserted into the peroneal nerve posterior to the fibular head and a reference electrode was inserted subcutaneously 1 to 3 cm from the recording electrode. The electrical signal was amplified, filtered, full-wave rectified, and integrated to obtain a full-voltage neurogram. HR, SBP, and DBP were continuously monitored with an automated sphygmomanometer (Escort 100, Medical Data Electronics). When a successful neurogram was obtained (for criteria, see Reference 19¹⁹ ), subjects rested quietly for 20 minutes to allow physiological measures to return to baseline. Then, subjects remained supine with their eyes open for a 10-minute baseline period, during which HR and BP were measured each minute and MSNA was recorded continuously with a physiological recorder (Windograph, model 40-8474, Gould). Mean resting HR, SBP, and DBP were calculated as the average of the 10 baseline measurements. MSNA was identified visually and expressed as the mean number of bursts per minute averaged over the 10-minute baseline period.¹⁹

Statistical Analysis
Statistical analyses were performed with the software of the SAS Institute. Measurements were compared between Pima Indians and whites by the use of general linear regression models with and without simultaneous adjustment for age and percent body fat. Simple correlation analyses were used to assess the relations among percent body fat, fasting insulin, MSNA, HR, and BP within each ethnic group. Partial correlation analyses and multiple regression analyses were used to examine the relation between different measures after adjustment for covariates and to assess whether the relations differ between Pima Indians and whites. Results are given as mean±SEM.

	Results

Top Abstract Introduction Methods Results Discussion References

 
The characteristics of the study population are given in the Table. On average, Pima Indians were shorter and heavier than whites and had a higher percent body fat. There were no ethnic differences in mean fasting and 2-hour plasma glucose concentrations, but the mean fasting plasma insulin concentration was higher in Pima Indians, a difference that remained significant (P<0.01) after adjustment for percent body fat. Pima Indians had lower MSNA, similar HR, and higher SBP and DBP as compared with whites. After adjustment for percent body fat, the ethnic difference in MSNA increased from 5 bursts/min (P<0.001) to 9 bursts/min (P<0.0001), whereas SBP and DBP were no longer different between the two groups.

Correlation Analyses
Adiposity
HR, SBP, and DBP were all positively related to percent body fat in both whites (HR: r=0.27, P<0.05; SBP: r=0.49, P<0.005; DBP: r=0.39, P<0.05) and Pima Indians (HR: r=0.25, P<0.05; SPB: r=0.30, P<0.01; DBP: r=0.22, P<0.07), as was the fasting insulin concentration (Figure 1). In contrast, MSNA was positively related to percent body fat in whites but not in Pima Indians (Figure 1, P<0.01 for an ethnic difference in the slopes of the regression lines). In whites, SBP and DBP but not HR remained significantly related to percent body fat after adjustment for MSNA (partial r=0.31, P<0.06; r=0.36, P<0.05; and r=0.14, NS, respectively). In Pima Indians, HR and SBP but not DBP remained significantly related to percent body fat after adjustment for MSNA (partial r=0.28, P<0.05; r=0.31, P<0.01; and r=0.18, NS, respectively).

View larger version (27K): [in this window] [in a new window]   Figure 1. Relations between percent body fat, fasting plasma insulin concentration, and resting MSNA in male normotensive whites (left panels) and Pima Indians (right panels).

Insulinemia
MSNA was positively related to fasting insulin concentration in whites but not in Pima Indians (Figure 1, P<0.01 for an ethnic difference in the slopes of the regression lines). In whites, the relation between MSNA and fasting insulin concentration remained significant after adjustment for percent body fat (partial r=0.34, P<0.05). Neither HR nor SBP and DBP were related to fasting insulin concentration in whites (Figure 2). In Pima Indians, SBP but neither HR nor DBP was positively related to fasting insulin concentration (Figure 2). The relation between SBP and fasting insulin concentration in Pima Indians was no longer significant after adjustment for percent body fat.

View larger version (27K): [in this window] [in a new window]   Figure 2. Relations between resting HR, systolic and diastolic BP, and fasting plasma insulin concentration in male normotensive whites (left panels) and Pima Indians (right panels).

MSNA
HR and SBP were positively related to MSNA in both whites and Pima Indians (Figure 3). DBP was positively related to MSNA in Pima Indians but not in whites.

View larger version (27K): [in this window] [in a new window]   Figure 3. Relations between resting HR, systolic and diastolic BP, and resting MSNA in male normotensive whites (left panels) and Pima Indians (right panels).

In multiple regression analyses with adjustment for age and ethnicity, percent body fat and MSNA were significant independent determinants of HR, SBP, and DBP. Together, these four factors explained 17%, 24%, and 25% of the variance (R²) in HR, SBP, and DBP, respectively. Fasting insulin concentration was not a significant determinant of either measure.

The ethnic differences in mean MSNA as well as in the relation between MSNA and percent body fat and insulinemia remained significant when MSNA was expressed as bursts/100 heartbeats, whereas SBP and DBP were no longer significantly related to MSNA in either ethnic group after the latter had been normalized for heart rate.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The results of the present study in normotensive white and Pima Indian men confirm the physiological importance of the SNS in normal BP regulation but indicate that the roles of hyperinsulinemia and increased SNS activity as links between obesity and BP can differ between different ethnicgroups. The lack of increase in MSNA with increasing adiposity and insulinemia in Pima Indians may explain, in part, why this population has a low propensity for hypertension despite the high prevalence of obesity and hyperinsulinemia.

Our results in whites seem to support Landsberg’s hypothesis,² because increased adiposity and elevated fasting plasma insulin concentrations were associated with increased MSNA and because MSNA in turn was positively correlated with HR and BP. The former observation agrees with findings from 2 previous microneurography studies,^{8 9} which also showed increased MSNA in obese whites. Other studies, however, have found conflicting results,^{13 14 15 16 27} bringing into question whether increased SNS activity is, in fact, a hallmark of human obesity.^{17 18} The finding that the fasting plasma insulin concentration was an additional determinant of MSNA in whites, independent of percent body fat, agrees with the study by Scherrer et al⁹ and is in keeping with experimental evidence that hyperinsulinemia may lead to increased SNS activity.¹⁰ However, our results also confirm the previous assumption² that hyperinsulinemia-induced SNS activation may not be the only link between obesity and elevated BP. First, MSNA remained significantly related to percent body fat after adjustment for the fasting insulin concentration, indicating that hyperinsulinemia is not the only and probably not the primary mechanism responsible for increased SNS activity in obese whites. Second, BP remained related to percent body fat after adjustment for MSNA, indicating that mechanisms other than hyperinsulinemia and increased SNS activity must be in place to mediate the association between obesity and BP. As recently reviewed,²⁸ these mechanisms might include obesity-related alterations in the structure and function of the cardiovascular system, in glomerular morphology and renal sodium excretion, and/or in leptin secretion and signaling.

Several previous studies have reported increased SNS activity in individuals with hypertension.^{29 30} Our results indicate that MSNA is positively correlated with HR and BP even within the normotensive range, confirming the physiological importance of SNS activity in normal BP regulation. Although the observed positive association between MSNA and HR agrees with findings by others,³¹ it is noteworthy that the positive association between MSNA and BP in the present study disappeared when MSNA was normalized for HR. This seems to support recent findings indicating that MSNA and HR may have interactive effects on BP.³² As with SNS activity, we³³ and others¹¹ have previously shown that BP increases with increasing insulinemia in whites. The fact that these findings could not be confirmed in the present study is probably due to the small number of subjects. Mechanisms other than increased SNS activity that could account for the association between insulinemia and BP include the effect of insulin on renal sodium excretion²⁸ and the resistance of vascular smooth muscle cells to the vasodilatory effect of insulin.³⁴

Our results in Pima Indians provide further interesting insights into the relation between adiposity, insulinemia, SNS activity, and BP. In agreement with previous findings,^{19 20 22 23 24} Pima Indian men were more obese and had markedly higher fasting plasma insulin concentrations than white men but had lower MSNA. This ethnic difference in MSNA appears to be largely attributable to the fact that MSNA does not increase with increasing adiposity in Pima Indians as it does in whites. Thus, low MSNA in Pima Indians does not seem to be an inherent characteristic but rather the result of a different SNS response to weight gain. This might be due, at least in part, to the dissociation between insulinemia and MSNA. Although insulinemia increases with increasing adiposity in Pima Indians, this is not accompanied by an increase in MSNA, as is the case in whites. Our findings in Pima Indians, therefore, indicate that hyperinsulinemia is not invariably associated with increased SNS activity, thus challenging Landsberg’s hypothesis.² It is possible that obese Pima Indians, who manifest resistance to the action of insulin on peripheral glucose uptake,^{23 24} also become resistant to the central effects of insulin to stimulate sympathetic outflow. However, MSNA does increase acutely in response to insulin infusion in Pima Indians,³⁵ suggesting that central SNS activation can be provoked. It has recently been suggested that MSNA may be increased primarily in those obese individuals who have obstructive sleep apnea.^{14 15} Although we did not test for the presence of sleep apnea in the present study, our clinical experience is that this condition is not less prevalent in obese Pima Indians than it is in obese whites. We have previously reported that in addition to having lower MSNA, Pima Indian men may also have lower ß-adrenergic sensitivity than whites.³⁶ In the present study, however, MSNA was positively related to HR and BP in Pima Indians and in whites, indicating that the low prevalence of hypertension in Pima Indians is probably not due to a resistance of the cardiovascular system to the stimulatory effect of the SNS. Rather, it appears that the lack of increase in MSNA with increasing adiposity and insulinemia in Pima Indians may contribute to their low propensity for hypertension. However, our data in normotensive subjects cannot ultimately prove this hypothesis.

While the direct measurement of MSNA by microneurography is highly reproducible and offers several advantages over indirect methods,³⁷ it only assesses postganglionic efferent sympathetic discharge rates to skeletal muscle and therefore does not allow for the determination of regional differences in SNS activity. These could be important, however, because recent evidence suggests that sympathetic overactivity in human obesity might be restricted to certain organs such as the kidneys.¹⁷ Furthermore, our conclusions are based on associative findings and warrant confirmation by intervention studies.

In summary, the present study indicates that in both whites and Pima Indians, HR and BP are positively and independently related to percent body fat and MSNA. However, MSNA is positively and independently related to percent body fat and insulinemia only in whites but not in Pima Indians. These results confirm the physiological importance of the SNS in normal BP regulation but indicate that the roles of hyperinsulinemia and increased SNS activity as mediators of the relation between obesity and BP can differ between different ethnic groups. The lack of increase in SNS activity with increasing adiposity and insulinemia in Pima Indians may contribute to the low prevalence of hypertension in this population.

	Acknowledgments

 
The authors wish to thank Dr James B. Young and Dr Arline D. Salbe for their helpful comments and careful review of the manuscript. We thank the volunteers for their participation and the nursing and dietary staff for the care of the volunteers. We also gratefully acknowledge the technical staff, particularly Linda Phillips, for assisting in the laboratory analyses.

Received February 28, 2000; first decision April 3, 2000; accepted May 4, 2000.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. NHLBI Obesity Education Initiative Expert Panel on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report. Obes Res. 1998;6(suppl 2):71S–82S.

2. Landsberg L. Diet, obesity and hypertension: an hypothesis involving insulin, the sympathetic nervous system, and adaptive thermogenesis. Q J Med. 1986;236:1081–1090.

3. Tuck ML. Obesity, the sympathetic nervous system, and essential hypertension. Hypertension. 1992;19(suppl I):I-67–I-77.

4. Brands MW, Hall JE, Van Vliet BN, Alonso-Galicia M, Herrera GA, Zappe D. Obesity and hypertension: roles of hyperinsulinemia, sympathetic nervous system, and renal mechanisms. J Nutr. 1995;125:1725S–1731S.

5. Modan M, HH, Almog S, Lusky A, Eshkol A, Shefi M, Shitrit A, Fuchs Z. Hyperinsulinemia: a link between hypertension, obesity, and glucose intolerance. J Clin Invest. 1985;75:809–817.

6. Masuo K, Mikami H, Ogihara T, Tuck ML. Familial hypertension, insulin, sympathetic activity, and blood pressure elevation. Hypertension. 1998;32:96–100.[Abstract/Free Full Text]

7. Troisi RJ, Weiss ST, Parker DR, Sparrow D, Young JB, Landsberg L. Relationship of obesity and diet to sympathetic nervous system activity. Hypertension. 1991;14:669–677.

8. Grassi G, Seravalle G, Cattaneo BM, Bolla GB, Lanfranchi A, Colombo M, Giannattasio C, Brunani A, Cavagnini F, Mancia G. Sympathetic activation in obese normotensive subjects. Hypertension. 1995;25:560–563.[Abstract/Free Full Text]

9. Scherrer U, Randin D, Tappy L, Vollenweider P, Jequier E, Nicod P. Body fat and sympathetic nerve activity in healthy subjects. Circulation. 1994;89:2634–2640.[Abstract/Free Full Text]

10. Anderson EA, Balon TW, Hoffman RP, Sinkey CA, Mark AL. Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans. Hypertension. 1992;19:621–627.[Abstract/Free Full Text]

11. Marigliano A, Tedde R, Sechi LA, Pala A, Pisanu G, Pacifico A. Insulinemia and blood pressure: relationships in patients with primary and secondary hypertension, and with or without glucose metabolism impairment. Am J Hypertens. 1990;3:521–526.[Medline] [Order article via Infotrieve]

12. Goldstein D, Kopin IJ. The autonomic nervous system and catecholamines in normal blood pressure control and in hypertension. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis, and Management. New York, NY: Raven Press; 1990:711–737.

13. Gudbjoernsdottir S, Lonnroth P, Bergmann Sverrisdottir Y, Wallin BG, Elam M. Sympathetic nerve activity and insulin in obese normotensive and hypertensive men. Hypertension. 1996;27:276–280.[Abstract/Free Full Text]

14. Narkiewicz K, Van de Borne P, Cooley RL, Dyken ME, Somers VK. Sympathetic activity in obese subjects with and without sleep apnea. Circulation. 1998;98:772–776.[Abstract/Free Full Text]

15. Rumantir MS, Vaz M, Jennings GL, Collier G, Kaye DM, Seals DR, Wiesner GH, Brunner-LaRocca HP, Esler M. Neural mechanisms in human obesity-related hypertension. J Hypertens. 1999;17:1125–1133.[Medline] [Order article via Infotrieve]

16. Mbanya JCN, Thomas TH, Wilkinson R, Alberti KGMM, Taylor R. Hypertension and hyperinsulinemia: a relationship in diabetes, but not in essential hypertension. Lancet. 1988;1:733–734.[Medline] [Order article via Infotrieve]

17. Grassi G. Debating sympathetic overactivity as a hallmark of human obesity: a pro’s position. J Hypertens. 1999;17:1059–1060.[Medline] [Order article via Infotrieve]

18. Somers VK. Debating sympathetic overactivity as a hallmark of human obesity: an opposing position. J Hypertens. 1999;17:1061–1064.[Medline] [Order article via Infotrieve]

19. Spraul M, Ravussin E, Fontvieille AM, Rising R, Larson DE, Anderson EA. Reduced sympathetic nervous activity: a potential mechanism predisposing to body weight gain. J Clin Invest. 1993;92:1730–1735.

20. Nelson RG, Sievers ML, Knowler WC, Swinburn BA, Pettitt DJ, Saad MF, Liebow IM, Howard BV, Bennett PH. Low incidence of fatal coronary heart disease in Pima Indians despite high prevalence of non-insulin-dependent diabetes. Circulation. 1990;81:987–995.[Abstract/Free Full Text]

21. Calhoun DA, Oparil S. Racial differences in the pathogenesis of hypertension. Am J Med Sci. 1995;310(suppl 1):S86–S90.

22. Saad MF, Knowler WC, Pettitt DJ, Nelson RG, Mott DM, Bennett PH. Insulin and hypertension: relationship to obesity and glucose intolerance in Pima Indians. Diabetes. 1990;39:1430–1435.[Abstract]

23. Lillioja S, Nyomba BL, Saad MF, Ferraro R, Castillo C, Bennett PH, Bogardus C. Exaggerated early insulin release and insulin resistance in a diabetes-prone population: a metabolic comparison of Pima Indians and Caucasians. J Clin Endocrinol Metab. 1991;73:866–876.[Abstract/Free Full Text]

24. Weyer C, Hanson R, Bogardus C, Pratley RE. A high fasting insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. Diabetes. In press.

25. Tataranni PA, Cizza G, Snitker S, Gucciardo F, Lotsikas A, Chrousos GP, Ravussin E. Hypothalamic-pituitary-adrenal axis and sympathetic nervous system activities in Pima Indians and Caucasians. Metabolism. 1999;48:395–399.[Medline] [Order article via Infotrieve]

26. Christin L, O’Connell M, Bogardus C, Danforth E Jr, Ravussin E. Norepinephrine turn-over and energy expenditure in Pima Indian and white men. Metabolism. 1993;42:723–729.[Medline] [Order article via Infotrieve]

27. Peterson HR, Rothschild M, Weinberg CR, Fell RD, McLeish KR, Pfeifer MA. Body fat and the activity of the autonomic nervous system. N Engl J Med. 1988;318:1077–1083.[Abstract]

28. Mikhail N, Golub M, Tuck ML. Obesity and hypertension. Prog Cardiovasc Dis. 1999;42:39–58.[Medline] [Order article via Infotrieve]

29. Yamada Y, Miyajima E, Tochikubo O, Matsukawa T, Ishii M. Age-related changes in muscle sympathetic nerve activity in essential hypertension. Hypertension. 1989;13:870–877.[Abstract/Free Full Text]

30. Anderson EA, Sinkey CA, Lawton WJ, Mark AL. Elevated sympathetic nerve activity in borderline hypertensive humans. Hypertension. 1989;14:177–183.[Abstract/Free Full Text]

31. Grassi G, Vailati S, Bertinieri G, Seravalle G, Stella ML, Dell’Oro R, Mancia G. Heart rate as a marker of sympathetic activity. J Hypertens. 1998;16:1635–1639.[Medline] [Order article via Infotrieve]

32. Narkiewicz K, Somers VK. Interactive effect of heart rate and muscle sympathetic nerve activity on blood pressure. Circulation. 1999;100:2514–2518.[Abstract/Free Full Text]

33. Saad MF, Lillioja S, Nyomba BL, Castillo C, Ferraro R, De Gregorio M, Ravussin E, Knowler WC, Bennett PH, Howard BV, Bogardus C. Racial differences in the relationship between blood pressure and insulin resistance. N Engl J Med. 1991;324:733–739.[Abstract]

34. Laakso M, Edelman SV, Brechtel G, Baron AD. Decreased effect of insulin to stimulate skeletal muscle blood flow in obese men: a novel mechanism for insulin resistance. J Clin Invest. 1990;85:1844–1852.

35. Spraul M, Ravussin E, Baron AD. Lack of relationship between muscle sympathetic nerve activity and skeletal muscle vasodilation in response to insulin infusion. Diabetologia. 1996;39:91–96.[Medline] [Order article via Infotrieve]

36. Tataranni PA, Christin L, Snitker S, Paolisso G, Ravussin E. Pima Indian males have lower ß-adrenergic sensitivity than Caucasian males. J Clin Endocrinol Metab. 1997;83:1260–1263.[Abstract/Free Full Text]

37. Grassi G, Esler M. How to assess sympathetic activity in humans. J Hypertens. 1999;17:719–734.[Medline] [Order article via Infotrieve]

This article has been cited by other articles:

				N. E Straznicky, G. W Lambert, K. Masuo, T. Dawood, N. Eikelis, P. J Nestel, M. T McGrane, J. A Mariani, F. Socratous, R. Chopra, et al. Blunted sympathetic neural response to oral glucose in obese subjects with the insulin-resistant metabolic syndrome Am. J. Clinical Nutrition, January 1, 2009; 89(1): 27 - 36. [Abstract] [Full Text] [PDF]

				J. Tank, K. Heusser, A. Diedrich, D. Hering, F. C. Luft, A. Busjahn, K. Narkiewicz, and J. Jordan Influences of Gender on the Interaction between Sympathetic Nerve Traffic and Central Adiposity J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4974 - 4978. [Abstract] [Full Text] [PDF]

				M. J. Joyner, N. Charkoudian, and B. G. Wallin A sympathetic view of the sympathetic nervous system and human blood pressure regulation Exp Physiol, June 1, 2008; 93(6): 715 - 724. [Abstract] [Full Text] [PDF]

				C. L. Gentile, J. S. Orr, B. M. Davy, and K. P. Davy Modest weight gain is associated with sympathetic neural activation in nonobese humans Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1834 - R1838. [Abstract] [Full Text] [PDF]

				F. Razak, S. S. Anand, H. Shannon, V. Vuksan, B. Davis, R. Jacobs, K. K. Teo, M. McQueen, S. Yusuf, and for the SHARE Investigators Defining Obesity Cut Points in a Multiethnic Population Circulation, April 24, 2007; 115(16): 2111 - 2118. [Abstract] [Full Text] [PDF]

				C. Shibao, A. Gamboa, A. Diedrich, A. C. Ertl, K. Y. Chen, D. W. Byrne, G. Farley, S. Y. Paranjape, S. N. Davis, and I. Biaggioni Autonomic Contribution to Blood Pressure and Metabolism in Obesity Hypertension, January 1, 2007; 49(1): 27 - 33. [Abstract] [Full Text] [PDF]

				N. Charkoudian, M. J. Joyner, L. A. Sokolnicki, C. P. Johnson, J. H. Eisenach, N. M. Dietz, T. B. Curry, and B. G. Wallin Vascular adrenergic responsiveness is inversely related to tonic activity of sympathetic vasoconstrictor nerves in humans J. Physiol., May 1, 2006; 572(3): 821 - 827. [Abstract] [Full Text] [PDF]

				R. J. Huggett, J. Burns, A. F. Mackintosh, and D. A.S.G. Mary Sympathetic Neural Activation in Nondiabetic Metabolic Syndrome and Its Further Augmentation by Hypertension Hypertension, December 1, 2004; 44(6): 847 - 852. [Abstract] [Full Text] [PDF]

				F. A. El-Atat, S. N. Stas, S. I. McFarlane, and J. R. Sowers The Relationship between Hyperinsulinemia, Hypertension and Progressive Renal Disease J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2816 - 2827. [Abstract] [Full Text] [PDF]

				G. F. DiBona The Sympathetic Nervous System and Hypertension: Recent Developments Hypertension, February 1, 2004; 43(2): 147 - 150. [Full Text] [PDF]

				A. Aneja, F. El-Atat, S. I. McFarlane, and J. R. Sowers Hypertension and Obesity Recent Prog. Horm. Res., January 1, 2004; 59(1): 169 - 205. [Abstract] [Full Text]

				J. Tank, J. Jordan, A. Diedrich, C. Schroeder, R. Furlan, A. M. Sharma, F. C. Luft, and G. Brabant Bound Leptin and Sympathetic Outflow in Nonobese Men J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4955 - 4959. [Abstract] [Full Text] [PDF]

				R. D. Brook, L. Glazewski, S. Rajagopalan, and R. L. Bard Hypertension and Triglyceride Catabolism: Implications for the Hemodynamic Model of the Metabolic Syndrome J. Am. Coll. Nutr., August 1, 2003; 22(4): 290 - 295. [Abstract] [Full Text] [PDF]

				B. Vozarova, C. Weyer, S. Snitker, J.-F. Gautier, G. Cizza, G. Chrousos, E. Ravussin, and P. A. Tataranni Effect of Cortisol on Muscle Sympathetic Nerve Activity in Pima Indians and Caucasians J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3218 - 3226. [Abstract] [Full Text] [PDF]

				N. I. Abate, Y. H. Mansour, M. Tuncel, D. Arbique, B. Chavoshan, A. Kizilbash, T. Howell-Stampley, W. Vongpatanasin, and R. G. Victor Overweight and Sympathetic Overactivity in Black Americans Hypertension, September 1, 2001; 38(3): 379 - 383. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Weyer, C. Articles by Tataranni, P. A. Search for Related Content PubMed PubMed Citation Articles by Weyer, C. Articles by Tataranni, P. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Obesity Related Collections Obesity Cerebrovascular disease/stroke Risk Factors Autonomic, reflex, and neurohumoral control of circulation