Increased Cardiac Sympathetic Drive and Reduced Vagal Modulation Following Endothelin Receptor Antagonism in Healthy Conscious Rats

Souza, Hugo Celso Dutra de; Terzini, Geisa C S V; Silva, Valdo J D da; Martins‐Pinge, Marli Cardoso; Salgado, Hélio César; Salgado, Maria-Cristina O

doi:10.1111/j.1440-1681.2008.04866.x

Cited by 13 publications

(13 citation statements)

References 35 publications

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“…Renal norepinephrine and renin expressions were also markedly increased, which would be also anticipated as a consequence of hyperleptinemia. The high-frequency domain of HRV, an index of vagal tone, 15 was reduced in the 90-day-old OffOb rats, suggesting impairments of the parasympathetic control, which could contribute to a further increase in blood pressure. In the time-domain parasympathetic indexes, SD of normal to normal intervals and root mean square of successive differences were also reduced, which corroborates the parasympathetic dysfunction shown by spectral analysis.…”

Section: Discussionmentioning

confidence: 99%

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Evidence for Sympathetic Origins of Hypertension in Juvenile Offspring of Obese Rats

et al. 2010

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Abstract-Maternal obesity in rodents is associated with increased adiposity, impaired glucose tolerance, and hypertension in adult offspring. In this study we investigated the influence of maternal obesity in the rat on blood pressure and blood pressure regulatory pathways in juvenile and adult offspring. Obesity was induced before pregnancy in female Sprague-Dawley rats by feeding a highly palatable energy-dense diet. In juvenile animals (30 days of age), before the onset of obesity and hyperleptinemia, basal nighttime mean arterial pressure was significantly raised in the offspring of obese dams (OffOb) relative to offspring of controls (OffCon; mean arterial pressure, males: OffOb, 121.8Ϯ0.6 mm Hg versus OffCon, 115.0Ϯ0.5 mm Hg, nϭ6, PϽ0.01; females: OffOb, 125.4Ϯ0.4 mm Hg versus OffCon, 114.4Ϯ0.5 mm Hg, nϭ6, PϽ0.001), as was the mean arterial pressure response to restraint stress (PϽ0.01). The pressor response to a leptin challenge was enhanced in OffOb rats (⌬mean arterial pressure: OffOb, 9.7Ϯ0.8 mm Hg versus OffCon, 5.3Ϯ1.3 mm Hg; nϭ8; PϽ0.05). Renal tissue norepinephrine content (PϽ0.001) and renin expression (PϽ0.05) were markedly raised. Analysis of heart rate variability revealed an increased low:high frequency ratio in OffOb versus OffCon rats (PϽ0.05). At 90 days, hypertension in OffOb rats persisted and was abolished by ␣1-and ␤-adrenergic blockade, and cardiovascular responses to phenylephrine or sodium nitroprusside indicated altered baroreceptor function. The exaggerated pressor response to leptin in OffOb rats was maintained. Hypertension in the offspring of obese rats may arise from persistent sympathoexcitatory hyperresponsiveness acquired in early stages of development. (Hypertension. 2010;55:76-82.)Key Words: hypertension Ⅲ sympathetic activity Ⅲ leptin Ⅲ developmental programming Ⅲ kidney T he influences of the worldwide obesity epidemic on reproductive health in women, particularly in relation to an adverse pregnancy outcome, present a significant health burden and a substantive healthcare cost. 1 We now appreciate that consequences for the child may extend well beyond the perinatal period. Evidence from observational cohort studies has suggested that maternal obesity is an independent determinant of childhood obesity and metabolic syndrome, arising from adverse influences of the maternal "hypernutritional" environment on the developing child; however, because of a multiplicity of confounding variables, causality cannot easily be proven. 2-5 Studies on experimental animals have provided the strongest evidence for a causal relationship. 2,6 -8 We have developed a rodent model of maternal obesity in mice 9 and rats 6 and have shown that adult offspring display many features of the metabolic syndrome, including hypertension at 3 months of age. 9 We reported recently that hyperphagia and increased adiposity in adult rat offspring are associated with resistance to the anorectic and weight-reducing actions of leptin, as well as impaired leptin signaling in the arcuate nucleus of the hypothala...

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Section: Discussionmentioning

confidence: 99%

“…High-frequency HR oscillations are generally mediated through parasympathetic pathways in rats. 15 The SD (SD of normal to normal intervals) and root mean square of successive differences, time domain parameters describing HRV, were also reduced in OffOb rats (Table; please see the online Data Supplement). …”

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Evidence for Sympathetic Origins of Hypertension in Juvenile Offspring of Obese Rats

et al. 2010

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“…The present findings indicate an important role for ET-1 in mediating the arterial baroreflex control of HR in normal animals. Previous studies have indicated that blockade of ET-1 is associated with depressed control of HR in normal animals (32). There is good evidence that ET receptors are present at multiple loci that affect baroreflex control including the carotid sinus, nucleus tractus solitarius (NTS), area postrema, and rostral ventrolateral medulla (RVLM) (24,28).…”

Section: Discussionmentioning

confidence: 99%

Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure

Abukar

May

Ramchandra

2016

American Journal of Physiology-Regulatory, Integrative and Comp

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Heart failure (HF) is associated with increased sympathetic nerve activity to the heart (CSNA), which is directly linked to mortality in HF patients. Previous studies indicate that HF is associated with high levels of plasma endothelin-1 (ET-1), which correlates with the severity of the disease. We hypothesized that blockade of endothelin receptors would decrease CSNA. The effects of intravenous tezosentan (a nonselective ETA and ETB receptor antagonist) (8 mg·kg−1·h−1) on resting levels of CSNA, arterial pressure, and heart rate were determined in conscious normal sheep ( n = 6) and sheep with pacing-induced HF ( n = 7). HF was associated with a significant decrease in ejection fraction (from 74 ± 2% to 38 ± 1%, P < 0.001) and a significant increase in resting levels of CSNA burst incidence (from 56 ± 11 to 87 ± 2 bursts/100 heartbeats, P < 0.01). Infusion of tezosentan for 60 min significantly decreased resting mean aterial pressure (MAP) in both normal and HF sheep (−8 ± 4 mmHg and −4 ± 3 mmHg, respectively; P < 0.05). This was associated with a significant decrease in CSNA (by 25 ± 26% of control) in normal sheep, but there was no change in CSNA in HF sheep. Calculation of spontaneous baroreflex gain indicated significant impairment of the baroreflex control of HR after intravenous tezosentan infusion in normal animals but no change in HF animals. These data suggest that endogenous levels of ET-1 contribute to the baseline levels of CSNA in normal animals, but this effect is absent in HF.

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“…ET present in the brain has been shown to regulate sympathetic nervous system [ 12 , 13 ] . It has been found that 7 day treatment with a non-selective ET A/B receptor antagonist, bosentan produced an increase in sympathetic drive and a decrease in parasympathetic activity indicating that endogenous ET plays an important role in sympathetic regulation [ 14 ] . We have previously reported that ET can modulate the pharmacological eff ects of adrenergic drugs such as clonidine [ 15 -17 ] .…”

Section: Repeated Administration Of Centhaquin To Pregnant Rats Did Nmentioning

confidence: 99%

Repeated Administration of Centhaquin to Pregnant Rats did not Affect Postnatal Development and Expression of Endothelin Receptors in the Brain, Heart or Kidney of Pups

Briyal

Lavhale²,

Gulati

2012

Arzneimittelforschung

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The effect of repeated administration of centhaquin to pregnant rats on postnatal development, and expression of ETA and ETB receptors was determined. Pregnant rats were treated daily with either saline or centhaquin for 2 weeks. Male rat pups were sacrificed on day 1, 7, 14 and 28 of birth. Brain, kidney and heart were removed to study the expression of ETA and ETB receptor protein levels. Body weight of pregnant rats increased steadily in both vehicle and centhaquin groups. Expression of ETA receptors in the heart and kidney was similar in vehicle and centhaquin treated postpartum rats, but was significantly increased in the brain of centhaquin treated postpartum rats. No change in expression of ETB receptors was observed. In postnatal rats, mean body weight and weights of the brain, kidney and heart increased proportionally with advancing age and were similar in vehicle and centhaquin groups. The expression of ETA receptors in the brain, heart and kidneys was similar in vehicle and centhaquin groups. ETB receptor expression significantly (p<0.001) decreased by 72% and 70% on day 28 compared to rats of age 1, 7 and 14 days in control and centhaquin groups, respectively. Centhaquin treated rats showed similar expression of ETA and ETB receptors compared to vehicle treatment. This study suggests that repeated administration of centhaquin was well tolerated by pregnant rats that gave birth to normal pups. Centhaquin did not affect postnatal development of rats and had similar expression of ETA and ETB receptors compared to control pups.

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Increased Cardiac Sympathetic Drive and Reduced Vagal Modulation Following Endothelin Receptor Antagonism in Healthy Conscious Rats

Cited by 13 publications

References 35 publications

Evidence for Sympathetic Origins of Hypertension in Juvenile Offspring of Obese Rats

Evidence for Sympathetic Origins of Hypertension in Juvenile Offspring of Obese Rats

Role of endothelin-1 in mediating changes in cardiac sympathetic nerve activity in heart failure

Repeated Administration of Centhaquin to Pregnant Rats did not Affect Postnatal Development and Expression of Endothelin Receptors in the Brain, Heart or Kidney of Pups

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