We studied the effects of a hypocaloric diet (D, n = 24, age: 32.2 +/- 1.4 yr, body mass index: 34.7 +/- 0.5 kg/m2) and a hypocaloric diet associated with exercise training (D + T, n = 25, age: 32.3 +/- 1.3 yr, body mass index: 32.9 +/- 0.4 kg/m2) on muscle metaboreflex control, muscle sympathetic nerve activity (MSNA, microneurography), blood pressure, and forearm blood flow (plethysmography) levels during handgrip exercise at 10% and 30% of maximal voluntary contraction in normotensive obese women. An additional 10 women matched by age and body mass index were studied as a nonadherent group. D or D + T significantly decreased body mass index. D or D + T significantly decreased resting MSNA (bursts/100 heartbeats). The absolute levels of MSNA were significantly lower throughout 10% and 30% exercise after D or D + T, although no change was found in the magnitude of response of MSNA. D + T, but not D, significantly increased resting forearm vascular conductance. D + T significantly increased the magnitude of the response of forearm vascular conductance during 30% exercise. D or D + T significantly increased MSNA levels during posthandgrip circulatory arrest when muscle metaboreflex is isolated. In conclusion, weight loss improves muscle metaboreflex control in obese women. Weight loss reduces MSNA, which seems to be centrally mediated. Weight loss by D + T increases forearm vascular conductance at rest and during exercise in obese individuals.

There is no information about the muscle metaboreflex control in obese individuals. In 40 normotensive obese women (OW; body mass index 33.5 +/- 0.4 kg/m2, age 32.4 +/- 1.1 yr) and 15 age-matched, normotensive lean women (LW; body mass index 22.7 +/- 0.8 kg/m2, age 34.4 +/- 1.4 yr), we measured muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) in the nonexercising forearm during static exercise at 10 and 30% of maximal voluntary contraction (MVC). Baseline MSNA (38 +/- 2 vs. 31 +/- 1 bursts/min, P = 0.001) and mean blood pressure were significantly higher in OW compared with LW. FBF was significantly lower, whereas forearm vascular resistance was significantly higher in OW. During 10% MVC, MSNA increased similarly in both groups, but during 30% MVC, MSNA was higher in LW. FBF and forearm vascular resistance responses during both 10 and 30% MVC were similar between groups. During posthandgrip circulatory arrest, MSNA remained significantly elevated compared with baseline in both groups, but this increase was significantly lower in OW (3.8 +/- 0.82 vs. 9.4 +/- 1.03 bursts/min, P = 0.002). In conclusion, muscle metaboreflex control of MSNA is blunted in OW. MSNA responses are not augmented during selective activation of central command/mechanoreceptors and metaboreceptors, despite increased MSNA levels in OW. Muscle vasodilatory response during graded handgrip isometric exercise is preserved in OW.

We hypothesized that the muscle vasodilatation during mental stress and exercise would vary among humans who are polymorphic at alleles 16 and 27 of the β2-adrenoceptors. From 216 preselected volunteers, we studied 64 healthy, middle-aged normotensive women selected to represent three genotypes: homozygous for the alleles Arg16 and Gln27 (Arg16/Gln27, n = 34), Gly16 and Gln27 (Gly16/Gln27, n = 20), and Gly16 and Glu27 (Gly16/Glu27, n = 10). Forearm blood flow (plethysmography) and muscle sympathetic nerve activity (microneurography) were recorded during 3-min Stroop color-word test and 3-min handgrip isometric exercise (30% maximal voluntary contraction). Baseline muscle sympathetic nerve activity, forearm vascular conductance, mean blood pressure, and heart rate were not different among groups. During mental stress, the peak forearm vascular conductance responses were greater in Gly16/Glu27 group than in Gly16/Gln27 and Arg16/Gln27 groups (1.79 ± 0.66 vs. 0.70 ± 0.11 and 0.58 ± 0.12 units, P = 0.03). Similar results were found during exercise (0.80 ± 0.25 vs. 0.28 ± 0.08 and 0.31 ± 0.08 units, P = 0.02). Further analysis in a subset of subjects showed that brachial intra-arterial propranolol infusion abolished the difference in vasodilatory response between Gly16/Glu27 ( n = 6) and Arg16/Gln27 ( n = 7) groups during mental stress (0.33 ± 0.20 vs. 0.46 ± 0.21 units, P = 0.50) and exercise (0.08 ± 0.06 vs. 0.03 ± 0.03 units, P = 0.21). Plasma epinephrine concentration in Arg16/Gln27 and Gly16/Glu27 groups was similar. In conclusion, women who are homozygous for Gly16/Glu27 of the β2-adrenoceptors have augmented muscle vasodilatory responsiveness to mental stress and exercise.

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To study the relationship between the sympathetic nerve activity and hemodynamic alterations in obesity, we simultaneously measured muscle sympathetic nerve activity (MSNA), blood pressure, and forearm blood flow (FBF) in obese and lean individuals. Fifteen normotensive obese women (BMI = 32.5 ± 0.5 kg/m 2 ) and 11 agematched normotensive lean women (BMI = 22.7 ± 1.0 kg/m 2 ) were studied. MSNA was evaluated directly from the peroneal nerve by microneurography, FBF was measured by venous occlusion plethysmography, and blood pressure was measured noninvasively by an autonomic blood pressure cuff. MSNA was significantly increased in obese women when compared with lean control women. Forearm vascular resistance and blood pressure were significantly higher in obese women than in lean women. FBF was significantly lower in obese women. BMI was directly and significantly correlated with MSNA, blood pressure, and forearm vascular resistance levels, but inversely and significantly correlated with FBF levels. Obesity increases sympathetic nerve activity and muscle vascular resistance, and reduces muscle blood flow. These alterations, taken together, may explain the higher blood pressure levels in obese women when compared with lean age-matched women. Obesity is associated with hypertension, diabetes and dyslipidemia, and, in consequence, cardiovascular disease (1-4). In obese individuals, the hyperinsulinemia provoked by insulin resistance increases sympathetic nerve activity, which seems to link obesity to high blood pressure. Interesting, however, is the fact that not all obese individuals are hypertensive. The hypertensive effect of obesity is lower in Pima Indians, Hispanic Americans and African Americans than it is in Whites (5,6). Besides, even among Whites, not all obese individuals are hypertensive. Therefore, it is likely that the levels of blood pressure may be related to the etiology of obesity and/or the genetic mechanisms of obesity (7,8).It has been described that obese individuals have vascular dysfunction. The peripheral blood flow (9) and the vasodilatory re-

Since neurovascular control is altered in obese subjects, we hypothesized that weight loss by diet (D) or diet plus exercise training (D + ET) would improve neurovascular control during mental stress in obese women. In a study with a dietary reduction of 600 kcal/day with or without exercise training for 4 months, 53 obese women were subdivided in D (N = 22, 33 +/- 1 years, BMI 34 +/- 1 kg/m2), D + ET (N = 22, 33 +/- 1 years, BMI 33 +/- 1 kg/m2), and nonadherent (NA, N = 9, 35 +/- 2 years, BMI 33 +/- 1 kg/m2) groups. Muscle sympathetic nerve activity (MSNA) was measured by microneurography and forearm blood flow by venous occlusion plethysmography. Mental stress was elicited by a 3-min Stroop color word test. Weight loss was similar between D and D + ET groups (87 +/- 2 vs 79 +/- 2 and 85 +/- 2 vs 76 +/- 2 kg, respectively, P < 0.05) with a significant reduction in MSNA during mental stress (58 +/- 2 vs 50 +/- 2, P = 0.0001, and 59 +/- 3 vs 50 +/- 2 bursts/100 beats, P = 0.0001, respectively), although the magnitude of the response was unchanged. Forearm vascular conductance during mental stress was significantly increased only in D + ET (2.74 +/- 0.22 vs 3.52 +/- 0.19 units, P = 0.02). Weight loss reduces MSNA during mental stress in obese women. The increase in forearm vascular conductance after weight loss provides convincing evidence for D + ET interventions as a nonpharmacologic therapy of human obesity.

Objective: We tested the hypothesis that muscle sympathetic nerve activity (MSNA) and forearm vascular resistance (FVR) would be augmented during mental stress or cold pressor test in healthy obese individuals compared with healthy lean individuals. Research Methods and Procedures: Twenty-nine healthy obese women and 12 age-matched healthy lean women were involved in the study. MSNA was directly measured from the peroneal nerve using microneurography. Forearm blood flow was measured by venous occlusion plethysmography. Blood pressure (BP) was monitored noninvasively by an automatic BP cuff, and heart rate (HR) was measured by electrocardiogram. Stroop color word test was performed for 4 minutes, and the cold pressor test was performed for 2 minutes. Results: Baseline MSNA and FVR were greater in the obese group than in the lean group. BP and HR were similar between groups. During mental stress, MSNA and FVR were greater in obese individuals than in lean individuals, although the magnitude of response was similar between groups. BP and HR similarly increased in obese and lean individuals. During the cold pressor test, MSNA, FVR, and BP were greater in obese individuals, but the magnitude of response was similar between groups. HR increased similarly during the cold pressor test in both obese and lean individuals. Discussion: Obesity increases MSNA and FVR during mental stress and the cold pressor test. This inappropriate neurovascular control can be expected to have an adverse effect on the risk factors for cardiovascular events and, hence, should be considered in the treatment of obese patients.

Objective: To investigate the association of short form (Glu 9 /Glu 9 ) of the 12Glu9 deletion polymorphism of the a 2B -adrenergic receptor (a 2B -AR) gene polymorphism with the cardiac autonomic responsiveness during sustained isometric handgrip exercise. Design: Cross-sectional clinical study. Subjects: In all, 97 normotensive obese women (body mass index (BMI) ¼ 33.2 kg/m 2 ). Of these, 78 (80.41%) were genotyped as Glu 12 /Glu 12 , 13 (13.40%) as Glu 12 /Glu 9 and six (6.19%) as Glu 9 /Glu 9 form. Measurements: The sympathovagal balance was assessed by means of power spectral analysis of heart rate variability at rest and during sustained isometric handgrip exercise at 30% of maximal voluntary handgrip contraction for 3 min. Two spectral components were analysed: low-frequency component reflecting sympathetic efferent activity and high-frequency power (HFnu) reflecting parasympathetic modulation. In addition, a normalized low-frequency power (LFnu) and HFnu were analysed. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. Results: There were no differences in baseline measurements among groups. The absolute level of LFnu throughout handgrip exercise was significantly lower in Glu 9 /Glu 9 subjects compared with other genotypes, while the decline of absolute HFnu was significantly smaller compared with Glu 12 /Glu 12 genotype. Conclusion: These findings suggest that 12Glu9 deletion polymorphism of the a 2B -AR gene (Glu 9 /Glu 9 genotype) might result in reduced autonomic responsiveness by altering cardiac sympathetic and vagal function during sustained handgrip exercise in normotensive obese women.