Conscious obese rats have impaired reflex bradycardia and enhanced norepinephrine sensitivity

Buñag, Ruben D.; Meyer, Mary Hockenberry; Vansell, Nichole R.; Kerecsen, Laszlo

doi:10.1152/ajpregu.1996.271.3.r654

Cited by 8 publications

(7 citation statements)

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“…The diminished tonic influences of the NTS and CVLM may explain the initially blunted HDZ-induced tachycardia observed in adult OZR in the present study, which is in agreement with previous reports of impaired rises in HR that focus on the initial responses observed with brief infusions of nitroprusside (3,37). Highlighting the relatively small magnitude of the deficit, several reports in obese rats fail to see significant differences in hypotension-induced tachycardia, even when hypertension-induced bradycardia is clearly attenuated (5,6,11,47). Regardless of the differences observed at the onset of hypotension, within minutes, HDZ-induced tachycardia was comparable in OZR and LZR, suggesting other mechanisms activated by hypotension provided a delayed compensation that allowed the OZR to effectively respond to a sustained decrease in MAP.…”

Section: * *supporting

confidence: 92%

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

Guimaraes

Huber

Campagnole‐Santos

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Adult obese Zucker rats (OZR; >12 wk) develop elevated sympathetic nerve activity (SNA) and mean arterial pressure (MAP) with impaired baroreflexes compared with adult lean Zucker rats (LZR) and juvenile OZR (6-7 wk). In adult OZR, baroreceptor afferent nerves respond normally to changes in MAP, whereas electrical stimulation of baroreceptor afferent fibers produces smaller reductions in SNA and MAP compared with LZR. We hypothesized that impaired baroreflexes in OZR are linked to reduced activation of brain stem sites that mediate baroreflexes. In conscious adult rats, a hydralazine (HDZ)-induced reduction in MAP evoked tachycardia that was initially blunted in OZR, but equivalent to LZR within 5 min. In agreement, HDZ-induced expression of c-Fos in the rostral ventrolateral medulla (RVLM) was comparable between groups. In contrast, phenylephrine (PE)-induced rise in MAP evoked markedly attenuated bradycardia with dramatically reduced c-Fos expression in the nucleus tractus solitarius (NTS) of adult OZR compared with LZR. However, in juvenile rats, PE-induced hypertension evoked comparable bradycardia in OZR and LZR with similar or augmented c-Fos expression in NTS of the OZR. In urethane-anesthetized rats, microinjections of glutamate into NTS evoked equivalent decreases in SNA, heart rate (HR), and MAP in juvenile OZR and LZR, but attenuated decreases in SNA and MAP in adult OZR. In contrast, microinjections of glutamate into the caudal ventrolateral medulla, a target of barosensitive NTS neurons, evoked comparable decreases in SNA, HR, and MAP in adult OZR and LZR. These data suggest that OZR develop impaired glutamatergic activation of the NTS, which likely contributes to attenuated baroreflexes in adult OZR.

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Section: * *supporting

confidence: 92%

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

Guimaraes

Huber

Campagnole‐Santos

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Obesity is a well‐established risk factor for human hypertension 4,5 and is known to increase blood pressure in many animal models, including dogs 33–35 and rabbits 36 . In rats, genetic models of obesity, including the Zucker rat, exhibit modest elevations in blood pressure, 19,37 whereas diet‐induced obesity frequently produces little change in blood pressure 9–11 . C57BL/6J mice have been reported to exhibit elevated tail‐cuff blood pressure following 3 months on a high‐fat diet 7 .…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, the slight blood pressure elevation demonstrated in the obese mice is not associated with tachycardia, which is a prominent cardiovascular response to diet-induced obesity in rat, rabbit, dog and human. 9,10,[33][34][35][36] The reduced HR in obese mice during baseline could be due, in part, to the observed decreases in locomotor activity, but a similar pattern of reduced HR was evident in the light phase, when activity levels are very low. Thus, autonomic mechanisms may also contribute.…”

Section: Cardiovascular Physiology In Diet-induced Obesitymentioning

confidence: 94%

“…Some reports suggest that these observations extend to rat and mouse models of obesity 6–8 . However, many studies using long‐term recordings from chronically instrumented rats generally report minimal increases in MAP with diet‐induced obesity 9–11 . Advances in radiotelemetry technology allow for the measurement of MAP and HR in the freely moving mouse 12,13 and for acquisition of long‐term beat‐to‐beat time series for analysis of cardiovascular variability in the time and frequency domains.…”

Section: Introductionmentioning

confidence: 99%

“…[6][7][8] However, many studies using long-term recordings from chronically instrumented rats generally report minimal increases in MAP with diet-induced obesity. [9][10][11] Advances in radiotelemetry technology allow for the measurement of MAP and HR in the freely moving mouse 12,13 and for acquisition of long-term beat-to-beat time series for analysis of cardiovascular variability in the time and frequency domains. Recent lines of evidence suggest that these approaches may provide reliable indices of autonomic function in mice.…”

Section: Introductionmentioning

confidence: 99%

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Diet‐induced obesity and cardiovascular regulation in C57BL/6J mice

Williams

Chambers

Roberts

et al. 2003

Clin Exp Pharma Physio

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1. In the present study, we determined the effect of diet-induced obesity on cardiovascular and metabolic regulation in mice at standard laboratory temperatures (ambient temperature (Ta) = 22 degrees C) and during exposure to thermoneutrality (Ta = 30 degrees C). 2. Male C57BL/6J (B6) mice fed a high-fat diet (HFF; n = 17) or chow (CHW; n = 14) for 15 weeks were surgically instrumented with telemetry devices, housed in metabolic chambers and assigned to either control or atenolol treatment (25 mg/kg per day in drinking water) to determine the effects of obesity on baseline cardiovascular function and on the responses to thermoneutrality and 24 h fasting. Mean arterial pressure (MAP), heart rate (HR), arterial pressure and HR variability (time and frequency domain), oxygen consumption (VO2) and locomotor activity were determined. 3. The HFF mice exhibited increased bodyweight (+10.6 +/- 4.1 g), moderate light period hypertension (+8.6 +/- 2.6 mmHg), no difference in HR and increased HR variability at standard laboratory temperature compared with CHW controls. Atenolol produced less of a decrease in HR in HFF mice (-42 +/- 10 b.p.m.) compared with CHW controls (-73 +/- 15 b.p.m.). Acute exposure to thermoneutrality (Ta = 30 degrees C) reduced HR similarly in both HFF and CHW mice (approximately 175 b.p.m.), but reduced MAP less in HFF than in CHW mice (-7.3 +/- 2.5 and -15.2 +/- 1.0 mmHg), respectively. Atenolol treatment had only minor effects on the HR response to thermonuetrality (-114 +/- 13 and -129 +/- 8 b.p.m. in HFF and CHW mice, respectively). The HFF mice displayed greater fasting-induced reductions in light period MAP than did CHW mice (-10.0 +/- 1.1 vs-3.1 +/- 3.5 mmHg, respectively), whereas HR was decreased equally in both groups. Fasting-induced increases in HR variability were attenuated in HFF mice. 4. We conclude that diet-induced obesity produced generally minor changes in cardiovascular regulation in B6 mice at baseline, some of which are distinct from the effects of diet-induced obesity in larger animal models. In contrast, acute variations in Ta or caloric availability produce pronounced alterations in cardiovascular function in either lean or obese mice, which are generally evident after atenolol and, thus, presumably not due exclusively to variation in cardiac sympathetic activity. Interestingly, the degree of obesity induced hypertension was augmented when mice were studied at thermonuetrality. The results suggest an important unrecognized role for vagal tone in the regulation of cardiovascular function in mice and support the need for considerable caution when using mouse models of obesity to examine regulation of cardiovascular function. We argue that mouse physiology studies should be performed in thermoneutral conditions.

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The enhanced hyperglycemic response to hemorrhage hypotension in obese rats is related to an impaired baroreflex

et al. 2008

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The aim of the present study was to assess the metabolic adjustments in adult rats with autonomic imbalance induced by hypercaloric diet. Male Wistar rats (4 weeks of age) were fed a chow diet (CD, n = 12) or hypercaloric diet (HD, n = 13) for 19 weeks. Body weight and dietary intake were measured every week and the basal metabolic rate was assessed. After 19 weeks of diet, six animals from each group were anesthetized with a lethal dose of barbital sodium (100 mg/Kg body weight, intraperitoneal; i.p.). Lee index was evaluated and adipose pads weighted. The remaining animals had a silastic cannula placed into the jugular vein for drug administration, blood collecting, and hemorrhage (1.2 mL/100 g bw/2 min). A polyethylene catheter (PE50) was inserted into the abdominal artery through the femoral artery for cardiovascular monitoring. The assessment of autonomic balance was done by evaluation of baroreflex sensitivity (intravenous (IV) injection of phenylephrine and sodium nitroprusside) and hemorrhage (1.2 mL/100 g bw/2 min). As expected, the HD induced obesity; increased weight gain (28%), adipose pads weight, and baroreflex dysfunction. The plasma level of free fatty acids and triacylglycerols were increased in HD rats by about 124% and 424%, respectively, as well as the basal metabolic rate measured at 19th weeks of diet (p < 0.01). We observed that baroreflex sensitivity to phenylephrine was reduced by about 50%, and the hyperglycemic response to hemorrhage hypotension was increased by 128% in HD rats. We found also a negative correlation between the alteration in baroreflex sensitivity and the increase in hyperglycemic response to hemorrhage in the obese rats (r = 0.72, p < 0.01) and a strong positive correlation between the increased Lee index and the hemorrhagic hyperglycemia (r = 0.93, p < 0.01). Our data demonstrate that obesity induced by hypercaloric diet in Wistar rats promotes an autonomic imbalance, which interferes with metabolic responses dependent on baroreflex sensitivity. In addition, we showed the existence of close correlation between the loss of baroreflex sensitivity and the degree of obesity.

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Conscious obese rats have impaired reflex bradycardia and enhanced norepinephrine sensitivity

Cited by 8 publications

References 0 publications

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

Development of attenuated baroreflexes in obese Zucker rats coincides with impaired activation of nucleus tractus solitarius

Diet‐induced obesity and cardiovascular regulation in C57BL/6J mice

The enhanced hyperglycemic response to hemorrhage hypotension in obese rats is related to an impaired baroreflex

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