16 research outputs found
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
Basal and ?-Adrenergic cardiomyocytes contractility dysfunction induced by dietary protein restriction is associated with downregulation of SERCA2a expression and disturbance of endoplasmic reticulum Ca2+ regulation in rats.
Background: The mechanisms responsible for the cardiac dysfunction associated with dietary protein restriction (PR) are poorly understood. Thus, this study was designed to evaluate the effects of PR on calcium kinetics, basal and ?-adrenergic contractility in murine ventricular cardiomyocytes. Methods: After breastfeeding male Fisher rats were distributed into a control group (CG, n = 20) and a protein-restricted group (PRG, n = 20), receiving isocaloric diets for 35 days containing 15% and 6% protein, respectively. Biometric and hemodynamic variables were measured. After euthanasia left ventricles (LV) were collected for histopathological evaluation, SERCA2a expression, cardiomyocytes contractility and Ca2+ sparks analysis. Results: PRG animals showed reduced general growth, increased heart rate and arterial pressure. These animals presented extracellular matrix expansion and disorganization, cardiomyocytes hypotrophy, reduced amplitudes of shortening and maximum velocity of contraction and relaxation at baseline and after ?-adrenergic stimulation. Reduced SERCA2a expression as well as higher frequency and lower amplitude of Ca2+ sparks were observed in PRG cardiomyocytes. Conclusion: The observations reveal that protein restriction induces marked myocardial morphofunctional damage. The pathological changes of cardiomyocyte mechanics suggest the potential involvement of the ?-adrenergic system, which is possibly associated with changes in SERCA2a expression and disturbances in Ca2+ intracellular kinetics
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
Neurotransmission of the Bezold-Jarisch reflex in the nucleus tractus solitarii of sino-aortic deafferentated rats.
The Bezold-Jarisch _B-J. reflex was activated by serotonin _5-HT, i.v.. before and 10 min after bilateral microinjection of increasing doses of kynurenic acid, a non-selective antagonist of excitatory amino acid _EAA. receptors, into the commissural nucleus tractus solitarii _NTS. of sino-aortic deafferentated _SAD. and sham-operated _SO. unanesthetized rats. Increasing doses of kynurenic acid produced a dose-dependent blockade of the bradycardic and hypotensive responses to B-J reflex activation in both SO _from 0.1 to 10.0 nmolr100 nl. and SAD _from 0.1 to 2.0 nmolr100 nl.. Comparison of the effect of kynurenic acid on the hypotension and bradycardic dose?response curves showed a significant difference between SO and SAD rats, indicating that smaller doses of kynurenic acid are required in SAD rats than in SO rats to block the neurotransmission of the B-J reflex in the NTS. The data also showed that bilateral microinjection of kynurenic acid into the NTS at doses of 0.5 _131"7 vs. 115"8 mmHg. and 2.0 nmolr100 nl _140"11 vs. 116"9 mmHg. produced an acute and significant increase in the basal mean arterial pressure of SAD rats similar to that observed with the same doses in SO rats, which was back to control values 5?10 min later. The increase in basal mean arterial pressure immediately after kynurenic acid microinjection into the NTS of SAD rats suggests that in the absence of the arterial baroreceptors, the B-J reflex plays an important role in the autonomic regulation of the circulation. The data also show different dose?response curves for hypotension and bradycardia in response to B-J reflex activation in SAD than in SO rats in the presence of increasing doses of kynurenic acid into the NTS, indicating that the neurotransmission of the B-J reflex in the NTS of SAD rats is more sensitive to the blockade of the EAA receptors than in SO rats
NMDA receptors in nucleus tractus solitarii are linked to soluble guanylate cyclase.
We sought to test the hypothesis that cardiovascular responses to
activation of ionotropic, but not metabotropic, glutamate receptors in
the nucleus tractus solitarii (NTS) depend on soluble guanylate
cyclase (sGC) and that inhibition of sGC would attenuate baroreflex
responses to changes in arterial pressure. In adult male Sprague-
Dawley rats anesthetized with chloralose, the ionotropic receptor
agonists N-methyl-D-aspartate (NMDA) and DL- -amino-3-hydroxy-
5-methylisoxazole-propionic acid (AMPA) and the metabotropic receptor
agonist trans-DL-amino-1,3-cyclopentane-dicarboxylic acid
(ACPD) were microinjected into the NTS before and after microinjection
of sGC inhibitors at the same site. Inhibition of sGC produced
significant dose-dependent attenuation of cardiovascular responses to
NMDA but did not alter responses produced by injection of AMPA or
ACPD. Bilateral inhibition of sGC did not alter arterial pressure, nor
did it attenuate baroreflex responses to pharmacologically induced
changes in arterial pressure. This study links sGC with NMDA, but
not AMPA or metabotropic, receptors in cardiovascular signal transduction
through NTS
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
Baroreflex function in conscious rats submitted to iron overload.
Our hypothesis is that iron accumulated in tissue, rather than in serum, may compromise cardiovascular control. Male Fischer 344 rats weighing 180 to 220 g were divided into 2 groups. In the serum iron overload group (SIO, N = 12), 20 mg elemental iron was injected ip daily for 7 days. In the tissue iron overload group (TIO, N = 19), a smaller amount of elemental iron was injected (10 mg, daily) for 5 days followed by a resting period of 7 days. Reflex heart rate responses were elicited by iv injections of either phenylephrine (0.5 to 5.0 ?g/kg) or sodium nitroprusside (1.0 to 10.0 ?g/kg). Baroreflex curves were determined and fitted to sigmoidal equations and the baroreflex gain coefficient was evaluated. To evaluate the role of other than a direct effect of iron on tissue, acute treatment with the iron chelator deferoxamine (20 mg/kg, iv) was performed on the TIO group and the baroreflex was re-evaluated. At the end of the experiments, evaluation of iron levels in serum confirmed a pronounced overload for the SIO group (30-fold), in contrast to the TIO group (2-fold). Tissue levels of iron, however, were higher in the TIO group. The SIO protocol did not produce significant alterations in the baroreflex curve response, while the TIO protocol produced a nearly 2-fold increase in baroreflex gain (-4.34 ? 0.74 and -7.93 ? 1.08 bpm/mmHg, respectively). The TIO protocol animals treated with deferoxamine returned to sham levels of baroreflex gain (-3.7 ? 0.3 sham vs -3.6 ? 0.2 bpm/mmHg) 30 min after the injection. Our results indicate an effect of tissue iron overload on the enhancement of baroreflex sensitivity
High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats.
Overweight and obesity are conditions associated with an overall range of clinical health consequences,
and they could be involved with the development of neuropsychiatric diseases, such as generalized anxiety
disorder (GAD) and panic disorder (PD). A crucial brain nuclei involved on the physiological functions
and behavioral responses, especially fear, anxiety and panic, is the dorsomedial hypothalamus (DMH).
However, the mechanisms underlying the process whereby the DMH is involved in behavioral changes
in obese rats still remains unclear. The current study further investigates the relation between obesity
and generalized anxiety, by investigating the GABAA sensitivity to pharmacological manipulation within
the DMH in obese rats during anxiety conditions. Male Wistar rats were divided in two experimental
groups: the first was fed a control diet (CD; 11% w/w) and second was fed a high fat diet (HFD; 45%
w/w). Animals were randomly treated with muscimol, a GABAA agonist and bicuculline methiodide (BMI),
a GABAA antagonist. Inhibitory avoidance and escape behaviors were investigated using the Elevated
T-Maze (ETM) apparatus. Our results revealed that the obesity facilitated inhibitory avoidance acquisition,
suggesting a positive relation between obesity and the development of an anxiety-like state. The
injection of muscimol (an anxiolytic drug), within the DMH, increased the inhibitory avoidance latency in
obese animals (featuring an anxiogenic state). Besides, muscimol prolonged the escape latency and controlling
the possible panic-like behavior in these animals. Injection of BMI into the DMH was ineffective
to produce an anxiety-like effect in obese animals opposing the results observed in lean animals. These
findings support the hypotheses that obese animals are susceptible to develop anxiety-like behaviors,
probably through changes in the GABAergic neurotransmission within the DMH