Brown adipose tissue thermogenesis precedes food intake in genetically obese Zucker (fa/fa) rats.

In Sprague?Dawley rats, brown adipose tissue (BAT) thermogenesis occurs in an episodic ultradianmanner (BAT on-periods) as part of the basic rest?activity cycle (BRAC). Eating occurs approximately 15 min after the onset of BAT on-periods. Zucker obese (fa/fa) rats eat larger less frequent meals than control rats. In chronically instrumented conscious unrestrained Zucker obese rats we examined ultradian fluctuations in BAT, body and brain temperatures, and the relation between BAT temperature and eating. The interval between BAT temperature peaks for the 12 hour dark phase was 121 ? 3 (mean ? SE) min for Zucker obese rats and 91 ? 3 min for control lean rats (p b 0.01). Corresponding values for the light phase were 148 ? 6 and 118 ? 4 min (p b 0.01).Mean BAT and body temperatures were lower in Zucker obese rats, in comparison with lean controls, during both BAT on-periods and BAT off-periods. Mean brain temperatures were lower during BAT off-periods. Amplitudes of the BRAC-related increases in all 3 temperatures were greater in the Zucker obese rats. Meal onset in Zucker obese rats commenced 15 ? 1 min after the onset of a BAT on-period, not significantly different for the delay observed in lean control rats (18 ? 1 min, p > 0.05). Thus periods between eating are increased in the Zucker obese rats, but the action of leptin, absent in these animals, is not crucial for the timing of eating in relation to increases in BAT and body temperature. Lack of the normal excitatory action of leptin on brain-regulated BAT sympathetic discharge could also contribute to lower BAT thermogenesis in Zucker obese rats

Role of the Renin Angiotensin System in Blood Pressure Allostasis-induced by Severe Food Restriction in Female Fischer rats

Severe food restriction (FR) is associated with blood pressure (BP) and cardiovascular dysfunction. The renin-angiotensin system (RAS) regulates BP and its dysregulation contributes to impaired cardiovascular function. Female Fischer rats were maintained on a control (CT) or severe FR (40% of CT) diet for 14 days. In response to severe FR, BP allostasis was achieved by up-regulating circulating Ang-[1-8] by 1.3-fold through increased angiotensin converting enzyme (ACE) activity and by increasing the expression of AT1Rs 1.7-fold in mesenteric vessels. Activation of the RAS countered the depressor effect of the severe plasma volume reduction (≥30%). The RAS, however, still underperformed as evidenced by reduced pressor responses to Ang-[1-8] even though AT1Rs were still responsive to the depressor effects of an AT1R antagonist. The aldosterone (ALDO) response was also inadequate as no changes in plasma ALDO were observed after the large fall in plasma volume. These findings have implications for individuals who have experienced a period(s) of severe FR (e.g., anorexia nervosa, dieters, natural disasters) and suggests increased activity of the RAS in order to achieve allostasis contributes to the cardiovascular dysfunction associated with inadequate food intake

Role of the renin angiotensin system in blood pressure allostasis-induced by severe food restriction in female Fischer rats.

Severe food restriction (FR) is associated with blood pressure (BP) and cardiovascular dysfunction. The renin-angiotensin system (RAS) regulates BP and its dysregulation contributes to impaired cardiovascular function. Female Fischer rats were maintained on a control (CT) or severe FR (40% of CT) diet for 14 days. In response to severe FR, BP allostasis was achieved by up-regulating circulating Ang-[1?8] by 1.3-fold through increased angiotensin converting enzyme (ACE) activity and by increasing the expression of AT1Rs 1.7-fold in mesenteric vessels. Activation of the RAS countered the depressor effect of the severe plasma volume reduction (?30%). The RAS, however, still underperformed as evidenced by reduced pressor responses to Ang-[1?8] even though AT1Rs were still responsive to the depressor effects of an AT1R antagonist. The aldosterone (ALDO) response was also inadequate as no changes in plasma ALDO were observed after the large fall in plasma volume. These findings have implications for individuals who have experienced a period(s) of severe FR (e.g., anorexia nervosa, dieters, natural disasters) and suggests increased activity of the RAS in order to achieve allostasis contributes to the cardiovascular dysfunction associated with inadequate food intake

New insights on amygdala : basomedial amygdala regulates the physiological response to social novelty.

The amygdala has been associated with a variety of functions linked to physiological, behavioral and endocrine responses during emotional situations. This brain region is comprised of multiple sub-nuclei. These subnuclei belong to the same structure, but may be involved in different functions, thereby making the study of each sub-nuclei important. Yet, the involvement of the basomedial amygdala (BMA) in the regulation of emotional states has yet to be defined. Therefore, the aim of our study was to investigate the regulatory role of the BMA on the responses evoked during a social novelty model and whether the regulatory role depended on an interaction with the dorsomedial hypothalamus (DMH). Our results showed that the chemical inhibition of the BMA by the microinjection of muscimol (c-aminobutyric acid (GABAA) agonist) promoted increases in mean arterial pressure (MAP) and heart rate (HR), whereas the chemical inhibition of regions near the BMA did not induce such cardiovascular changes. In contrast, the BMA chemical activation by the bilateral microinjection of bicuculline methiodide (BMI; GABAA antagonist), blocked the increases in MAP and HR observed when an intruder rat was suddenly introduced into the cage of a resident rat, and confined to the small cage for 15 min. Additionally, the increase in HR and MAP induced by BMA inhibition were eliminated by DMH chemical inhibition. Thus, our data reveal that the BMA is under continuous GABAergic influence, and that its hyperactivation can reduce the physiological response induced by a social novelty condition, possibly by inhibiting DMH neurons

Tobacco-free cigarette smoke exposure induces anxiety and panic-related behaviours in male wistar rats.

Smokers, who generally present with lung damage, are more anxious than non-smokers and have an associated augmented risk of panic. Considering that lung damage signals specific neural pathways that are related to affective responses, the aim of the present study was to evaluate the influence of pulmonary injury on anxiety and panic-like behaviours in animals exposed to cigarette smoke with and without tobacco. Male Wistar rats were divided into the following groups: a control group (CG); a regular cigarette group (RC); and a tobacco-free cigarette (TFC) group. Animals were exposed to twelve cigarettes per day for eight consecutive days. The animals were then exposed to an elevated T-maze and an open field. The RC and TFC groups presented increases in inflammatory cell inflow, antioxidant enzyme activity, and TBARS levels, and a decrease in the GSH/GSSG ratio was observed in the TFC group. Exposure to RC smoke reduced anxiety and panic-related behaviours. On the other hand, TFC induced anxiety and panic-related behaviours. Thus, our results contradict the concept that nicotine is solely accountable for shifted behavioural patterns caused by smoking, in that exposure to TFC smoke causes anxiety and panic-related behaviours.Cigarette smoke exposure is associated with anxiety states. Smokers are more anxious than non-smokers1, while cigarette smoking cessation is associated with increased levels of anxiety and stress, as the nicotine in cigarettes has been shown to have anxiolytic effects2. Moreover, smoking is also associated with an augmented risk of panic attacks, and quitting smoking could help reduce this risk3. Importantly, in a study conducted by Amaring and colleagues, it was reported that 72% of panic disorder patients declared that they were regular smokers at the onset of their disease4. Cigarette smoke is also one of the several agents and environmental factors that can trigger oxidative stress and pulmonary damage5. Cigarette smoke causes cellular recruitment, lipid peroxidation, production of inflammatory mediators, and oxidative stress6?11. For instance, studies in mice have shown that exposure to short-term cigarette smoke evokes an increase in inflammatory cell inflow and oxidative damage6,9. In general, exposure to pollutants induces pulmonary inflammation through the generation of oxidative stress12,13, defined as the imbalance in reactive oxygen species production, to the detriment of the antioxidant defence systems14. Importantly, exposure to ambient air particles not only induces pulmonary inflammation but also behavioural disorders both in humans and in mice15. Currently, the majority of anxiety studies associated with cigarette smoking have focused on the anxiolytic effects of nicotine2. However, it has been shown that lung damage can induce central nervous system responses by activating specific neuronal pathways16,17, which include those linked to affective responses, such as anxiety and panic18. This raises the question of whether the anxiety and panic-type behaviour associated with smoking might be related not only to the nicotine or to tobacco?s other constituents but also to lung damage

Chronic treatment with ivabradine does not affect cardiovascular autonomic control in rats.

A low resting heart rate (HR) would be of great benefit in cardiovascular diseases. Ivabradine-a novel selective inhibitor of hyperpolarization-activated cyclic nucleotide gated (HCN) channels- has emerged as a promising HR lowering drug. Its effects on the autonomic HR control are little known. This study assessed the effects of chronic treatment with ivabradine on the modulatory, reflex and tonic cardiovascular autonomic control and on the renal sympathetic nerve activity (RSNA). Male Wistar rats were divided in 2 groups, receiving intraperitoneal injections of vehicle (VEH) or ivabradine (IVA) during 7 or 8 consecutive days. Rats were submitted to vessels cannulation to perform arterial blood pressure (AP) and HR recordings in freely moving rats. Time series of resting pulse interval and systolic AP were used to measure cardiovascular variability parameters. We also assessed the baroreflex, chemoreflex and the Bezold-Jarish reflex sensitivities. To better evaluate the effects of ivabradine on the autonomic control of the heart, we performed sympathetic and vagal autonomic blockade. As expected, ivabradine-treated rats showed a lower resting (VEH: 362 ? 16 bpm vs. IVA: 260 ? 14 bpm, p = 0.0005) and intrinsic HR (VEH: 369 ? 9 bpm vs. IVA: 326 ? 11 bpm, p = 0.0146). However, the chronic treatment with ivabradine did not change normalized HR spectral parameters LF (nu) (VEH: 24.2 ? 4.6 vs. IVA: 29.8 ? 6.4; p > 0.05); HF (nu) (VEH: 75.1 ? 3.7 vs. IVA: 69.2 ? 5.8; p > 0.05), any cardiovascular reflexes, neither the tonic autonomic control of the HR (tonic sympathovagal index; VEH: 0.91? 0.02 vs. IVA: 0.88 ? 0.03, p = 0.3494). We performed the AP, HR and RSNA recordings in urethane-anesthetized rats. The chronic treatment with ivabradine reduced the resting HR (VEH: 364 ? 12 bpm vs. IVA: 207 ? 11 bpm, p < 0.0001), without affecting RSNA (VEH: 117 ? 16 vs. IVA: 120 ? 9 spikes/s, p = 0.9100) and mean arterial pressure (VEH: 70 ? 4 vs. IVA: 77 ? 6 mmHg, p = 0.3293). Our results suggest that, in health rats, the long-term treatment with ivabradine directly reduces the HR without changing the RSNA modulation and the reflex and tonic autonomic control of the heart

Brown adipose tissue thermogenesis precedes food intake in genetically obese Zucker (fa/fa) rats.

In Sprague–Dawley rats, brown adipose tissue (BAT) thermogenesis occurs in an episodic ultradianmanner (BAT on-periods) as part of the basic rest–activity cycle (BRAC). Eating occurs approximately 15 min after the onset of BAT on-periods. Zucker obese (fa/fa) rats eat larger less frequent meals than control rats. In chronically instrumented conscious unrestrained Zucker obese rats we examined ultradian fluctuations in BAT, body and brain temperatures, and the relation between BAT temperature and eating. The interval between BAT temperature peaks for the 12 hour dark phase was 121 ± 3 (mean ± SE) min for Zucker obese rats and 91 ± 3 min for control lean rats (p b 0.01). Corresponding values for the light phase were 148 ± 6 and 118 ± 4 min (p b 0.01).Mean BAT and body temperatures were lower in Zucker obese rats, in comparison with lean controls, during both BAT on-periods and BAT off-periods. Mean brain temperatures were lower during BAT off-periods. Amplitudes of the BRAC-related increases in all 3 temperatures were greater in the Zucker obese rats. Meal onset in Zucker obese rats commenced 15 ± 1 min after the onset of a BAT on-period, not significantly different for the delay observed in lean control rats (18 ± 1 min, p > 0.05). Thus periods between eating are increased in the Zucker obese rats, but the action of leptin, absent in these animals, is not crucial for the timing of eating in relation to increases in BAT and body temperature. Lack of the normal excitatory action of leptin on brain-regulated BAT sympathetic discharge could also contribute to lower BAT thermogenesis in Zucker obese rats

SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating.

SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating. Am J Physiol Regul Integr Comp Physiol 301: R987–R994, 2011. First published August 3, 2011; doi:10.1152/ajpregu.00085.2011.—Brown adipose tissue (BAT) thermogenesis occurs episodically in an ultradian manner approximately every 80–100 min during the waking phase of the circadian cycle, together with highly correlated increases in brain and body temperatures, suggesting that BAT thermogenesis contributes to brain and body temperature increases. We investigated this in conscious Sprague-Dawley rats by determining whether inhibition of BAT thermogenesis via blockade of beta-3 adrenoceptors with SR59230A interrupts ultradian episodic increases in brain and body temperatures and whether SR59230A acts on BAT itself or via sympathetic neural control of BAT. Interscapular BAT (iBAT), brain, and body temperatures, tail artery blood flow, and heart rate were measured in unrestrained rats. SR59230A (1, 5, or 10 mg/kg ip), but not vehicle, decreased iBAT, body, and brain temperatures in a dose-dependent fashion (log-linear regression P 0.01, R2 0.3, 0.4, and 0.4, respectively, n 10). Ultradian increases in BAT, brain, and body temperature were interrupted by administration of SR59230A (10 mg/kg ip) compared with vehicle, resuming after 162 24 min (means SE, n 10). SR59230A (10 mg/kg ip) caused a transient bradycardia without any increase in tail artery blood flow. In anesthetized rats, SR59230A reduced cooling-induced increases in iBAT temperature without affecting cooling-induced increases in iBAT sympathetic nerve discharge. Inhibition of BAT thermogenesis by SR59230A, thus, reflects direct blockade of beta-3 adrenoceptors in BAT. Interruption of episodic ultradian increases in body and brain temperature by SR59230A suggests that BAT thermogenesis makes a substantial contribution to these increases

The dorsomedial hypothalamus and the central pathways involved in the cardiovascular response to emotional stress.

Psychological stress elicits increases in sympathetic activity accompanied by a marked cardiovascular response. Revealing the relevant central mechanisms involved in this phenomenon could contribute significantly to our understanding of the pathogenesis of stress-related cardiovascular diseases, and the key to this understanding is the identification of the nuclei, pathways and neurotransmitters involved in the organization of the cardiovascular response to stress. The present review will focus specifically on the dorsomedial hypothalamus, a brain region now known to play a primary role in the synaptic integration underlying the cardiovascular response to emotional stress

The implication of protein malnutrition on cardiovascular control systems in rats.

The malnutrition in early life is associated with metabolic changes and cardiovascular impairment in adult hood. Deficient protein intake-mediated hypertension has been observed in clinical and experimental studies. In rats, protein malnutrition also increases the blood pressure and enhances heart rate and sympathetic activity. In this review, we discuss the effects of post-weaning protein malnutrition on the resting mean arterial pressure and heartrate and their variabilities, cardiovascular reflexes sensitivity, cardiac autonomic balance, sympathetic and renin-angiotensin activities and neural plasticity during adult life. These insights reveal an interesting prospect on the autonomic modulation underlying the cardiovascular imbalance and provide relevant information preventing cardiovascular diseases