Adrenergic and reflex abnormalities in obesity-related hypertension

Previous studies have shown that essential hypertension and obesity are both characterized by sympathetic activation coupled with a baroreflex impairment. The present study was aimed at determining the effects of the concomitant presence of the 2 above-mentioned conditions on sympathetic activity as well as on baroreflex cardiovascular control. In 14 normotensive lean subjects (aged 33. 5+/-2.2 years, body mass index 22.8+/-0.7 kg/m(2) [mean+/-SEM]), 16 normotensive obese subjects (body mass index 37.2+/-1.3 kg/m(2)), 13 lean hypertensive subjects (body mass index 24.0+/-0.8 kg/m(2)), and 16 obese hypertensive subjects (body mass index 37.5+/-1.3 kg/m(2)), all age-matched, we measured beat-to-beat arterial blood pressure (by Finapres device), heart rate (HR, by ECG), and postganglionic muscle sympathetic nerve activity (MSNA, by microneurography) at rest and during baroreceptor stimulation and deactivation induced by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. Blood pressure values were higher in lean hypertensive and obese hypertensive subjects than in normotensive lean and obese subjects. MSNA was significantly (P:<0.01) greater in obese normotensive subjects (49.1+/-3.0 bursts per 100 heart beats) and in lean hypertensive subjects (44.5+/-3.3 bursts per 100 heart beats) than in lean normotensive control subjects (32.2+/-2.5 bursts per 100 heart beats); a further increase was detectable in individuals with the concomitant presence of obesity and hypertension (62.1+/-3. 4 bursts per 100 heart beats). Furthermore, whereas in lean hypertensive subjects, only baroreflex control of HR was impaired, in obese normotensive subjects, both HR and MSNA baroreflex changes were attenuated, with a further attenuation being observed in obese hypertensive patients. Thus, the association between obesity and hypertension triggers a sympathetic activation and an impairment in baroreflex cardiovascular control that are greater in magnitude than those found in either of the above-mentioned abnormal conditions alone

Effects of hypertension and obesityon the sympathetic activation of heart failure patients

Previous studies have shown that congestive heart failure is characterized by sympathetic and reflex dysfunctions. Whether these alterations are potentiated in the presence of obesity and hypertension, two conditions that also display neuroadrenergic abnormalities and markedly increase the risk of heart failure, is unknown. In 14 healthy control subjects (C; age, 55.1±3.0 years; mean±SEM), 13 lean hypertensive subjects (H), 15 obese normotensive subjects (O), 14 lean normotensive subjects with congestive heart failure (CHF, New York Heart Association class II), 14 lean hypertensive subjects with CHF (CHFH), 14 obese normotensive subjects with CHF (CHFO), and 13 obese hypertensive subjects with CHF (CHFOH), all age-matched with C, we measured mean blood pressure (Finapres), heart rate (ECG), and muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during baroreflex testing. Compared with C, body mass index was similarly increased in O, CHFO, and CHFOH, whereas mean blood pressure was similarly increased in HF, CHFH, and CHFOH, and left ventricular ejection fraction (echocardiography) was similarly reduced in CHF, CHFH, CHFO and CHFOH. Compared with C, MSNA was significantly increased in O, H, and CHF (43.0±2.2 versus 54.1±2.8, 53.1±2.5, and 57.4±2.8 bursts/100 heart beats, P<0.01). When O or H was combined with CHF, the MSNA increase was significantly more pronounced and maximal when O and H were concomitantly associated with CHF. Baroreflex sensitivity was reduced in O and H, with a further reduction in CHF and a minimal value in CHFOH. These data show that the sympathetic activation characterizing CHF is markedly potentiated when O and H alone or combined together are associated with a low cardiac output state and that this may depend on an arterial baroreflex impairment

Sympathetic regulation of vascular function in health and disease.

The sympathetic nervous system (SNS) is known to play a pivotal role in short- and long-term regulation of different functions of the cardiovascular system. In the past decades increasing evidence demonstrated that sympathetic neural control is involved not only in the vasomotor control of small resistance arteries but also in modulation of large artery function. Sympathetic activity and vascular function, both of which are key factors in the development and prognosis of cardiovascular events and disease, are linked at several levels. Evidence from experimental studies indicates that the SNS is critically influenced, at the central and also at the peripheral level, by the most relevant factors regulating vascular function, such as nitric oxide (NO), reactive oxygen species (ROS), endothelin (ET), the renin-angiotensin system. Additionally, there is indirect evidence of a reciprocal relationship between endothelial function and activity of the SNS. A number of cardiovascular risk factors and diseases are characterized both by increased sympathetic outflow and decreased endothelial function. In healthy subjects, muscle sympathetic nerve activity (MSNA) appears to be related to surrogate markers of endothelial function, and an acute increase in sympathetic activity has been associated with a decrease in endothelial function in healthy subjects. However, direct evidence of a cause-effect relationship from human studies is scanty. In humans large artery stiffness has been associated with increased sympathetic discharge, both in healthy subjects and in renal transplant recipients. Peripheral sympathetic discharge is also able to modulate wave reflection. On the other hand, large artery stiffness can interfere with autonomic regulation by impairing carotid baroreflex sensitivit

Multiple sampling improves norepinephrine reproducibility in essential hypertension : a comparison with the microneurographic technique

Objectives Plasma norepinephrine displays a limited ability to reflect the enhanced sympathetic drive characterizing essential hypertension. Among the factors responsible, an important one is the reduced reproducibility of the norepinephrine approach. The present study aimed to determine whether increasing the number of blood samples on which norepinephrine assay is based improves norepinephrine reproducibility. This was done by taking muscle sympathetic nerve traffic recording as 'gold standard', which is characterized by an elevated short- and long-term reproducibility. Methods In 14 untreated mild-to-moderate essential hypertensive patients, we evaluated, in two experimental sessions spaced each other by a 10-14-day interval, blood pressure (Finapres), heart rate (ECG), plasma norepinephrine (HPLC) and muscle sympathetic nerve traffic (microneurography, peroneal nerve). In the two sessions, three norepinephrine samples were obtained at 30-min intervals between each. Norepinephrine reproducibility between sessions was assessed on a single norepinephrine sample or averaging together the values obtained from second or third samples. Reproducibility of norepinephrine data was then compared with the microneurographic one. Results Although muscle sympathetic nerve traffic values showed a highly significant correlation between sessions (r=0.79, P < 0.001), norepinephrine values derived from a single blood sample did not correlate with each other (r=0.42, PUNS). Norepinephrine correlation coefficients were consistently improved and achieved statistical significance when average data from second or third blood samples were examined (r=0.63, P < 0.03). Conclusion In essential hypertension, the reproducibility of plasma norepinephrine as an adrenergic marker can be substantially improved by performing a norepinephrine assay on multiple blood samples

Excessive sympathetic activation in heart failure with obesity and metabolic syndrome : characteristics and mechanisms

Congestive heart failure is characterized by sympathetic activation, which has also been described in the metabolic syndrome. No information exists, however, as to whether the sympathostimulating effects of these 2 conditions summate when heart failure is complicated by the metabolic syndrome, leading to an exceedingly high adrenergic drive. This is clinically relevant, because in heart failure sympathetic activation is closely related to mortality. We studied 48 control subjects (age: 58.4 +/- 1.6 years, mean +/- SEM) and 89 age-matched heart failure patients (New York Heart Association class II), of whom 47 were without and 42 were with metabolic syndrome. Measurements included blood pressure (Finapres), heart rate (ECG), and sympathetic nerve traffic (microneurography) at rest and during baroreceptor manipulation. Waist circumference, blood pressure, and metabolic variables were greater in heart failure with metabolic syndrome than in heart failure without metabolic syndrome and in control subjects. Left ventricular ejection fraction and end-diastolic diameter were similarly altered in the 2 heart failure groups. Compared with control subjects, sympathetic nerve activity was greater in heart failure patients without metabolic syndrome (64.7 +/- 3.2 versus 45.8 +/- 2.9 bursts/100 heartbeats; P < 0.01), a further pronounced increase being detected in those with metabolic syndrome (80.9 +/- 3.2 bursts/100 heartbeats; P < 0.01). In the multivariate analysis, waist circumference and body mass index were the variables most closely related to sympathetic activation. Compared with control subjects, baroreflex responses were significantly attenuated in the 2 heart failure groups, the impairment being more marked in the group with than without metabolic syndrome. Thus, obesity and metabolic syndrome potentiate the sympathetic activation characterizing heart failure. This potentiation is likely to mainly depend on metabolic and baroreflex mechanisms

Impact of the metabolic syndrome on subcutaneous microcirculation in obese patients

AB Objectives: Patients with the metabolic syndrome are at increased cardiovascular risk and display an augmented wall stiffness of the large-sized and medium-sized arteries, coupled with an endothelial dysfunction. Whether this is the case also for the small resistance arteries is unknown, however. It is also unknown whether and to what extent the hypothesized microvascular alterations are greater for magnitude than the ones characterizing obesity, that is the most common component of the metabolic syndrome. Methods: In 14 lean healthy controls (age 48.7 +/- 2.4 years, mean +/- SEM), 13 obese participants and 12 individuals with the metabolic syndrome (Adult Treatment Panel III criteria), all age-matched with healthy controls, we assessed the small resistance arteries dissected from the abdominal subcutaneous tissue on a pressurized myograph. Results: The media thickness, media cross-sectional area (CSA) and media-to-lumen ratio (M/L) of the small resistance arteries were markedly and significantly greater in metabolic syndrome than in controls (media thickness: 28.3 +/- 0.7 vs. 17.5 +/- 0.3 [mu]m; CSA: 24 760.8 +/- 1459 vs. 16 170.7 +/- 843.6 [mu]m2 and M/L: 0.12 +/- 0.01 vs. 0.064 +/- 0.002 a.u., respectively, P < 0.01 for all). Acetylcholine-induced relaxation was impaired in the vessels from metabolic syndrome participants compared with the lean healthy individuals (-48.8%, P < 0.01), whereas endothelium-independent vasorelaxation was similar in the two groups. The structural and functional microvascular alterations seen in metabolic syndrome were slightly, although not significantly, greater than the ones seen in uncomplicated obese participants. Stiffness of small arteries, as assessed by the stress/strain relationship, was also similar in the three groups of participants. Conclusion: Thus, metabolic syndrome is characterized by marked alterations in the structural and functional patterns of the small resistance arteries. These alterations, which are only slightly greater than the ones seen in obesity, may be responsible for the increased incidence of coronary and cerebrovascular events reported in metabolic syndrome

Heart rate as a sympathetic marker during acute adrenergic challenge

Objective: Previous studies have shown that heart rate has a limited value in reflecting the chronic state of adrenergic overdrive characterizing several cardiovascular diseases. Whether this also applies to the ability of heart rate to reflect acute and generalized changes in sympathetic activity is unknown. Methods: In 20 healthy young subjects (age: 25.2 \ub1 1.2 years, mean \ub1 SEM) we measured beat-to-beat blood pressure (Finapres), heart rate (HR, ECG), venous plasma norepinephrine (NE, high-performance liquid chromatography) and efferent postganglionic muscle sympathetic nerve traffic (MSNA, microneurography) at rest and during a cold pressor test and two intravenous infusions of nitroprusside at increasing doses. Results: Both cold pressor test and nitroprusside infusions triggered marked and significant increases in HR, plasma NE and MSNA; blood pressure showing an increase with cold pressor test and a reduction with nitroprusside. The magnitude of the responses was greater with the higher than with the lower dose of nitroprusside. The HR changes induced by cold pressor test were not significantly related to the concomitant NE and MSNA changes (r = -0.08 and r = -0.18, P = NS). This was also the case for the lower and the higher dose of nitroprusside (NE: r = -0.11 and r = 0.08; MSNA: r = 0.01 and r = -0.11, P = NS for all). In contrast NE and MSNA changes induced by cold pressor test and by the lower and the higher dose of nitroprusside were significantly related to each other (r = 0.70, r = 0.89 and r = 0.79 respectively, P < 0.01 for all). Conclusions: In a given individual, HR responses to sympathetic challenge do not quantitatively reflect the degree of acute and generalized adrenergic activation. Qualitative information on the acute adrenergic effects of given stimuli should thus be based on the assessment of NE and MSNA rather than on HR changes