Reactive oxygen species (ROS) have been shown to modulate neuronal synaptic transmission and may play a role on the autonomic control of the cardiovascular system. In this study we investigated the effects produced by hydrogen peroxide (H(2)O(2)) injected alone or combined with the anti-oxidant agent N-acetil-l-cysteine (NAC) or catalase into the fourth brain ventricle (4th V) on mean arterial pressure and heart rate of conscious rats. Moreover the involvement of the autonomic nervous system on the cardiovascular responses to H(2)O(2) into the 4th V was also investigated. Male Holtzman rats (280-320 g) with a stainless steel cannula implanted into the 4th V and polyethylene cannulas inserted into the femoral artery and vein were used. Injections of H(2)O(2) (0.5, 1.0 and 1.5 micromol/0.2 microL, n=6) into the 4th V produced transient (for 10 min) dose-dependent pressor responses. The 1.0 and 1.5 micromol doses of H(2)O(2) also produced a long lasting bradycardia (at least 24 h with the high dose of H(2)O(2)). Prior injection of N-acetyl-l-cysteine (250 nmol/1 microL/rat) into the 4th V blockade the pressor response and attenuated the bradycardic response to H(2)O(2) (1 micromol/0.5 microL/rat, n=7) into the 4th V. Intravenous (i.v.) atropine methyl bromide (1.0 mg/kg, n=11) abolished the bradycardia but did not affect the pressor response to H(2)O(2). Prazosin hydrochloride (1.0 mg/kg, n=6) i.v. abolished the pressor response but did not affect the bradycardia. The increase in the catalase activity (500 UEA/1 microL/rat injected into the 4th V) also abolished both, pressor and bradycardic responses to H(2)O(2). The results suggest that increased ROS availability into 4th V simultaneously activate sympathetic and parasympathetic outflow inducing pressor and bradycardic responses.

New Findings: What is the central question of this study?Is the increase in blood pressure observed in rats fed a low protein diet due to overactivation of sympathetic and renin angiontensin systems? What is the main finding and its importance?The data show an increase in the expression of angiotensin II type 1 receptors and an incrased sympathetic activity in this experimental model, suggesting that both systems are contributing to the high blood pressure observed in these animals. 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 (AT₁) receptor antagonist losartan alone or in combination with the α₁‐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 AT₁ 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 AT₁ receptors.

Psidium guajava (guava) leaves extract displays anti-hypertensive properties by mechanisms not yet fully understood. Here, we investigated whether sympathetic drive and immune signaling mechanisms are involved with the antihypertensive effect of the guava extract in a model of salt-dependent hypertension. Raw guava extract (rPsE) was characterized by colorimetric and UPLC-MS techniques. Two doses of rPsE (100 and 200 mg/kg) were evaluated for anti-hypertensive effect using a suspension system (PsE). Weaned male Wistar rats were put on a high-salt diet (HSD, 0.90 % Na⁺) for 16 weeks and received gavages of PsE for the last 4 weeks. Blood pressure (BP) was measured at the end of treatment in conscious rats. The neurogenic pressor effect was assessed by ganglionic blockade with hexamethonium. Autonomic modulation of heart rate was evaluated by spectral analysis. The effects of orally administered PsE on lumbar sympathetic nerve activity (LSNA) were assessed in anesthetized rats. Blood IL-10, IL-17A, and TNF were measured. The increased neurogenic pressor effect of HSD rats was reduced by PsE 100 mg/kg, but not by 200 mg/kg. PsE (200 mg/kg) administration in anesthetized rats produced a greater fall in BP of HSD rats compared to standard salt diet (SSD) rats. PsE hypotensive response elicited an unproportionable increase in LSNA of HSD rats compared to SSD rats. PsE (200 mg/kg) increased plasma concentrations of IL-10 but had no effect on TNF or IL-17A. Our data indicate that the antihypertensive effects of PsE may involve autonomic mechanisms and immunomodulation by overexpression of IL-10 in salt-dependent hypertensive rats.

Background: Physical training (ET) is important to restore the reflex sensitivity involved in controlling blood pressure in various diseases. Recent investigations have demonstrated an interaction between cardiopulmonary baroreceptors and arterial baroreflex during dynamic exercise.Objective: Considering that acute and chronic hemodynamic responses to swimming (SW) are different from the race (RUN), the objective of this study was to evaluate the effect of SW and RUN on baroreflex response before and after acute volume expansion in spontaneously hypertensive rats (SHR).Methods: SHR were divided into three groups: RUN, SW and sedentary (SED) groups. After training, the mean arterial pressure (MAP) and heart rate (HR) were recorded. Baroreflex response was assessed before and after acute volume expansion.Results: Both ET conditions reduced basal levels of HR and MAP. The first volume of injected isotonic saline solution (1.25% of body weight) produced a greater decrease in HR for the SW group (−105.8 ± 8.7 bpm) compared to RUN groups (−68 ± 5.2 bpm) and SED (−49.8 ± 7.2 bpm). Both training modalities increase the baroreflex response in relation to the SED group, but after the total volume expansion, the SW group presented attenuated response (0.7 ± 0.1 μPIms/mmHg) compared to RUN (1.5 ± 0.17 PIms/mmHg) and was not different from SED group (0.8 ± 0.2 mPIms/mmHg).Conclusion: The results show that the swim-trained group has a different baroreflex response to that observed by the run-trained group after the activation of the load receptors by saline expansion. Graphical abstract