Thermoregulatory responses, heart rate, and the susceptibility to anxiety in obese animals subjected to stress.

Obesity and stress are related to cardiovascular diseases. Rats fed a high-fat diet (HFD) show increased cardiovascular reactivity to emotional stress and altered defensive behavioral responses. Indeed, changes in thermoregulatory responses in an aversive environment are observed in these animals. However, studies aimed at clarifying the physiological mechanisms linking obesity, stress hyperreactivity and behavioral changes are needed. The aim of this study was to evaluate the changes in thermoregulatory responses, heart rate, and the susceptibility to anxiety in obese animals subjected to stress. Nine-week high-fat diet protocol was effective in inducing obesity by increasing weight gain, fat mass, adiposity index, white epididymal, retroperitoneal, inguinal and brown adipose tissue. Animals induced to obesity and subjected to stress (HFDS group) by the intruder animal method showed increases in heart rate (HR), core body temperature and tail temperature. HFDS showed an increase in the first exposure to the closed arm (anxiety-like behavior) in elevated T-Maze (ETM). The groups did not differ with respect to panic behavior assessed in the ETM and locomotor activity in the open field test. Our study shows that HFDS animals presented increased reactivity to stress with higher stress hyperthermia and anxious behavior. Thus, our results present relevant information regarding stress responsiveness and behavioral changes in obese animals.

Cardiovascular effects of small peptides of the renin angiotensin system.

The renin-angiotensin system (RAS) is a unique hormonal cascade which is composed by multiple enzymes and effector peptides. Recently, new peptides presenting biological activity have been discovered, increasing the complexity of the RAS Here, we evaluated the effects of small peptides of the RAS in coronary bed of rats. Firstly, we examined the direct effect of small angiotensinergic peptides [Angiotensin (Ang) -(1-5), Ang-(1-4) Ang-(1-3), and Ang-(1-2)] in coronary vessels. Noteworthy, it was observed that Ang-(1-4), Ang-(1-3), and Ang-(1-2) caused a significant reduction in pressure perfusion. Because Ang-(1-2) was the smallest peptide tested and presented the major effect, we decided to investigate its mechanisms of action. The effect of Ang-(1-2) was partially dependent on the Mas receptor, nitric oxide release and angiotensin-converting enzyme. Importantly, Ang-(1-2) reduced the blood pressure of Wistar rats and SHR Interestingly, SHR presented a more pronounced decrease in blood pressure levels than Wistar rats. Altogether, these data showed that angiotensinergic small peptides hold biological activities in coronary bed of rats.

Increased activity of the renin-angiotensin and sympathetic nervous systems is required for regulation of the blood pressure in rats fed a low-protein diet.

Previous studies have shown that postweaning protein restriction induces changes in the sympathetic nervous system in rats, leading to alterations in cardiovascular parameters. In addition, the renin-angiotensin system is also affected in these animals. Here, we hypothesized that adjustments in the interaction between the RAS and SNS underlie the cardiovascular adaptations observed in rats fed a low-protein diet. Thus, we evaluated the alterations in the mean arterial pressure (MAP) and heart rate of Fisher rats fed a protein-deficient diet before and after systemic administration of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II (Ang II) type 1 (AT(1)) receptor antagonist losartan alone or in combination with the α(1)-adrenergic receptor antagonist prazosin. Administration of enalapril or losartan decreased the MAP only of rats under protein restriction. Prazosin injection after the infusion of losartan caused a further decrease in the MAP of malnourished rats. In contrast, only the administration of prazosin elicited a reduction in the MAP of control animals. When the sequence of administration of the antagonists was inverted, infusion of prazosin in animals fed the standard or the low-protein diet induced a reduction in the MAP that was further decreased by the subsequent injection of losartan. Importantly, in both protocols the responses of malnourished animals to losartan were markedly greater when compared with the control group. Moreover, these animals presented lower levels of circulating Ang II and a reduced responsiveness to Ang II. In contrast, the expression of AT(1) receptors in the aorta of malnourished animals was increased. Thus, our data suggest that the renin-angiotensin system is an important factor supporting blood pressure in rats fed a low-protein diet and that the sympathetic nervous system activity in these animals is under strong influence of Ang II acting via AT(1) receptors.

Activation of 5-HT receptors in the periaqueductal gray attenuates the tachycardia evoked from dorsomedial hypothalamus.

Studies have shown that the dorsomedial hypothalamus (DMH) is a key region in the descending pathways mediating the cardiovascular response to emotional stress. We have recently demonstrated that the lateral/dorsolateral periaqueductal gray (l/dlPAG) is an important synaptic relay in mediating the tachycardic effect produced by activation of DMH neurons. This synaptic relay is mediated via NMDA excitatory amino acid receptors. In this study, our aim was to investigate, in conscious rats, whether activation of 5-Hydroxytriptamine 1A (5-HT(1A)) receptors in the l/dlPAG can attenuate the increases in heart rate and arterial pressure evoked by a) chemical activation of the DMH, b) air jet stress paradigm and c) chemical activation of l/dlPAG. Microinjections of the 5-HT(1A) receptor agonist, 8-OH-DPAT (1 nmol/100 nl), into the l/dlPAG reduced (by 62%) the increases in heart rate evoked by chemical activation of DMH neurons with the GABA(A) antagonist bicuculline methiodide (10 pmol/100 nl). The tachycardic and pressor responses evoked by air jet stress paradigm were also attenuated after treatment with 8-OH-DPAT in the l/dlPAG. The increases in heart rate and arterial pressure produced by microinjection of the excitatory amino acid receptor agonist, NMDA, into the l/dlPAG were largely reduced (by 94% and 73%, respectively) after treatment in the same region with 8-OH-DPAT. Taken together, our findings indicate that 5-HT(1A) receptors at the lateral dorsolateral PAG play a significant role in modulating the descending cardiovascular pathways from the dorsomedial hypothalamus and consequently the cardiovascular response to emotional stress.

Role of periaqueductal gray on the cardiovascular response evoked by disinhibition of the dorsomedial hypothalamus.

Activation of neurons in the region of the dorsomedial hypothalamus (DMH), by microinjection of the GABA(A) receptor antagonist bicuculline methiodide (BMI) results in increases in arterial pressure, heart rate as well as behavioral changes similar to those evoked by acute emotional stress. Previous anatomic studies clearly demonstrated projections from the DMH to the midbrain periaqueductal gray (PAG), a brain region implicated in the organization of behavioral strategies associated with specific cardiovascular responses. In this study, physiological experiments in conscious rats were used to investigate the functional significance of this pathway. Unilateral inhibition of the lateral dorsolateral region of the PAG (l/dlPAG) with the GABA(A) receptor agonist, muscimol (1 nmol/100 nl) largely reduced the tachycardia and the pressor response produced by microinjection of BMI (10 pmol/100 nl) into the ipsilateral DMH. In contrast, inhibition of the ventrolateral PAG (vlPAG) region had no significant effect on the cardiovascular response evoked from disinhibition of the ipsilateral DMH. Our present results indicate that the l/dlPAG region is an important synaptic relay in the descending cardiovascular pathways from the DMH.