Nitrergic pathways and L-type calcium channel of MnPO influencing cardiovascular homeostasis

The median preoptic nucleus (MnPO) is one of most important site of the lamina terminalis implicated in the regulation of hydro electrolytic and cardiovascular balance. The purpose of this study was to determine the effect of L-Type calcium channel antagonist, nifedipine, on the increase of median arterial blood pressure (MAP) induce by angiotensin II (ANG II) injected into the MnPO. The influence of nitric oxide (NO) on nifedipine antipressor action has also been studied by utilizing N W-nitro-L-arginine methyl ester (L-NAME) (40 μg 0.2 μL -1) a NO synthase inhibitor (NOSI), 7-nitroindazole (7-NIT) (40 μg 0.2 μL -1), a specific neuronal NO synthase inhibitor (nNOSI) and sodium nitroprusside (SNP) (20 μg 0.2 μL -1) a NO donor agent. We have also investigated the central role of losartan and PD123349 (20 nmol 0.2 μL -1), AT 1 and AT 2, respectively (selective non peptide ANG II receptor antagonists), in the pressor effect of ANG II (25 pmol 0.2 μL -1) injected into the MnPO. Male Wistar rats weighting 200-250 g, with cannulae implanted into the MnPO were utilized. Losartan injected into the MnPO, prior to ANG II, blocked the pressor effect of ANGII. PD 123319 only decreased the pressor effect of ANG II. Rats pre-treated with either 50 μg 0.2 μL -1 or 100 μg 0.2 μL -1 of nifedipine, followed by 25 pmol 0.2 μL -1 of ANG II, decreased ANG II-pressor effect. L-NAME potentiated the pressor effect of ANG II. 7-NIT injected prior to ANG II into the MnPO also potentiated the pressor effect of ANGII but with less intensity than that of L-NAME. SNP injected prior to ANG II blocked the pressor effect of ANG II. The potentiation action of L-NAME and 7-NIT on ANG II-pressor effect was blocked by prior injection of nifedipine. The results described in this study provide evidence that calcium channels play important roles in central ANG II-induced pressor effect. The structures containing NO in the brain, such as MnPO, include both endothelial and neuronal cells, which might be responsible for the influence of nifedipine on the pressor effect of ANG II. These data have shown the functional relationship between L-Type calcium channel and a free radical gas NO in the MnPO, on the control of ANG II-induced pressor effect acting in AT 1 and AT 2 receptors.

Efeitos da angiotensina II no sistema cardiovascular

Angiotensin is an important peptide of renin-angiotensin-aldosterone system. This peptide has an important function on arterial blood pressure regulation and body fluid homeostasis. However, its action on abnormal conditions causes deleterious effects on the cardiovascular system. Vascular resistance, hypertension, vascular and myocytes hipertrophy, production of free radicals and pro-inflammatory substances are some of the actions of angiotensin II that can result on cardiovascular remodeling. Angiotensinconverting enzyme (ACE) inhibitors, angiotensin receptors antagonists, antiinflammatories and antioxidants are used clinically and/or experimentally to prevent or reduce the effects of angiotensin II. The purpose of this work is to review the actions and interactions of angiotensin II on the cardiovascular system, as well as the therapeutic measures employed for the control of these effects.

Sidestream cigarette smoke and cardiac autonomic regulation

Background: The literature has already demonstrated that cigarette influences the cardiovascular system. In this study, we performed a literature review in order to investigate the relationship between sidestream cigarette smoke (SSCS) and cardiac autonomic regulation. Methods. Searches were performed on Medline, SciELO, Lilacs and Cochrane databases using the crossing between the key-words: cigarette smoking, autonomic nervous system, air pollution and heart rate variability. Results: The selected studies indicated that SSCS exposure affects the sympathetic and parasympathetic responses to changes in arterial blood pressure. Moreover, heart rate responses to environmental tobacco smoke are increased in smokers compared to non-smokers. The mechanism involved on this process suggest increased oxidative stress in brainstem areas that regulate the cardiovascular system. Conclusion: Further studies are necessary to add new elements in the literature to improve new therapies to treat cardiovascular disorders in subjects exposed to sidestream cigarette smoke. © 2013 Valenti et al; licensee BioMed Central Ltd.

Relationship between cardiac autonomic regulation and auditory mechanisms: Importance for growth and development

The literature has already demonstrated that auditory stimulation with music influences the cardiovascular system. In this study, we performed a literature review in order to investigate the relationship between auditory mechanisms and cardiac autonomic regulation. The selected studies indicated that there is a strong correlation between noise intensity and vagal-sympathetic balance. Also, it was reported that music therapy improved heart rate variability in anthracycline-treated breast cancer patients. It was hypothesized that dopamine release in the striatal system induced by pleasure songs are involved in the cardiac autonomic regulation. Further studies are necessary to add new elements in the literature to improve new therapies to treat cardiovascular disorders.

The effects of different styles of musical auditory stimulation on cardiac autonomic regulation in healthy women

The literature investigated the effects of chronic baroque music auditory stimulation on the cardiovascular system. However, it lacks in the literature the acute effects of different styles of music on cardiac autonomic regulation. To evaluate the acute effects of baroque and heavy metal music on heart rate variability (HRV) in women. The study was performed in 21 healthy women between 18 and 30 years old. We excluded persons with previous experience with music instrument and those who had affinity with the song styles. All procedures were performed in the same sound-proof room. We analyzed HRV in the time (standard deviation of normal-to-normal respiratory rate (RR) intervals, root-mean square of differences between adjacent normal RR intervals in a time interval, and the percentage of adjacent RR intervals with a difference of duration greater than 50 ms) and frequency (low frequency [LF], high frequency [HF], and LF/HF ratio) domains. HRV was recorded at rest for 10 min. Subsequently they were exposed to baroque or heavy metal music for 5 min through an earphone. After the first music exposure they remained at rest for more 5 min and them they were exposed again to baroque or heavy metal music. The sequence of songs was randomized for each individual. The power analysis provided a minimal number of 18 subjects. Shapiro-Wilk to verify normality of data and analysis of variance for repeated measures followed by the Bonferroni test for parametric variables and Friedman's followed by the Dunn's post-test for non-parametric distributions. During the analysis of the time-domain indices were not changed. In the frequency-domain analysis, the LF in absolute units was reduced during the heavy metal music stimulation compared to control. Acute exposure to heavy metal music affected the sympathetic activity in healthy women.

Vocal complaint in physical education teachers and its association with the cardiovascular system

Background: We examined the vocal complaints and evaluated the correlation between the vocal handicap index (VHI) and heart rate variability (HRV) in physical education teachers. We evaluated 46 teachers. Method: The subjects were investigated regarding voice complaint and the VHI was applied. HRV was recorded at seated rest for ten minutes and it was analyzed in the time, frequency domains, geometric indices and fractal exponents. The three domains of the VHI were correlated with the indices of HRV. Results: The physical education teachers presented a VHI score much below the standard of the physiological normality. There was correlation of the organic domain of the VHI with the NN50 and pNN50 and correlation of the functional domain and organic domain of the VHI with the HF index of HRV. Conclusion: The physical education teachers evaluated reported vocal complaints that affected their function and it is suggested to be related with the cardiac autonomic regulation.

Cardiovascular Responses Induced by Catalase Inhibitior into the Fourth Cerebral Ventricle is Changed in Wistar Rats Exposed to Sidestream Cigarette Smoke

Objectives: This experimental study aimed to evaluate the effects of central catalase inhibition on cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS) for 3 weeks. Methodology: A total of 20 males Wistar rats (320–370g) were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4thV). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS for three weeks, 180 minutes per day, 5 days/week [carbon monoxide (CO): 100–300 ppm)]. Baroreflex was tested with one pressor dose of phenylephrine (PHE, 8 μg/kg, bolus) and one depressor dose of sodium nitroprusside (SNP, 50 μg/kg, bolus). Cardiovascular responses were evaluated before and 15 minutes after 3-amino-1, 2, 4-triazole (ATZ, catalase inhibitor, 0.001g/100μL) injection into the 4th V. Results: Vehicle treatment into the 4th V did not change cardiovascular responses. Central catalase inhibition increased tachycardic peak, attenuated bradycardic peak and reduced HR range at 15 minutes, increased MAP at 5, 15 and 30 min and increased HR at 5 and 15 min. In rats exposed to SSCS, central ATZ increased basal MAP after 5 min and increased HR at 5, 15 and 30 minutes, respectively, and attenuated bradycardic peak at 15 minutes. Conclusion: This study suggests that brain oxidative stress caused by SSCS influences autonomic regulation of the cardiovascular system.

Cardiac autonomic regulation during exposure to auditory stimulation with classical baroque or heavy metal music of different intensities

Objectives: The effects of chronic music auditory stimulation on the cardiovascular system have been investigated in the literature. However, data regarding the acute effects of different styles of music on cardiac autonomic regulation are lacking. The literature has indicated that auditory stimulation with white noise above 50 dB induces cardiac responses. We aimed to evaluate the acute effects of classical baroque and heavy metal music of different intensities on cardiac autonomic regulation. Study design: The study was performed in 16 healthy men aged 18-25 years. All procedures were performed in the same soundproof room. We analyzed heart rate variability (HRV) in time (standard deviation of normal-to-normal R-R intervals [SDNN], root-mean square of differences [RMSSD] and percentage of adjacent NN intervals with a difference of duration greater than 50 ms [pNN50]) and frequency (low frequency [LF], high frequency [HF] and LF/HF ratio) domains. HRV was recorded at rest for 10 minutes. Subsequently, the volunteers were exposed to one of the two musical styles (classical baroque or heavy metal music) for five minutes through an earphone, followed by a five-minute period of rest, and then they were exposed to the other style for another five minutes. The subjects were exposed to three equivalent sound levels (60- 70dB, 70-80dB and 80-90dB). The sequence of songs was randomized for each individual. Results: Auditory stimulation with heavy metal music did not influence HRV indices in the time and frequency domains in the three equivalent sound level ranges. The same was observed with classical baroque musical auditory stimulation with the three equivalent sound level ranges. Conclusion: Musical auditory stimulation of different intensities did not influence cardiac autonomic regulation in men.

Acute auditory stimulation with different styles of music influences cardiac autonomic regulation in men

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of the gadolinium ion on body fluid regulation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Acute auditory stimulation with different styles of music influences cardiac autonomic regulation in men

No clear evidence is available in the literature regarding the acute effect of different styles of music on cardiac autonomic control. The present study aimed to evaluate the acute effects of classical baroque and heavy metal musical auditory stimulation on Heart Rate Variability (HRV) in healthy men. In this study, HRV was analyzed regarding time (SDNN, RMSSD, NN50, and pNN50) and frequency domain (LF, HF, and LF / HF) in 12 healthy men. HRV was recorded at seated rest for 10 minutes. Subsequently, the participants were exposed to classical baroque or heavy metal music for five minutes through an earphone at seated rest. After exposure to the first song, they remained at rest for five minutes and they were again exposed to classical baroque or heavy metal music. The music sequence was random for each individual. Standard statistical methods were used for calculation of means and standard deviations. Besides, ANOVA and Friedman test were used for parametric and non-parametric distributions, respectively. While listening to heavy metal music, SDNN was reduced compared to the baseline (P = 0.023). In addition, the LF index (ms(2) and nu) was reduced during exposure to both heavy metal and classical baroque musical auditory stimulation compared to the control condition (P = 0.010 and P = 0.048, respectively). However, the HF index (ms(2)) was reduced only during auditory stimulation with music heavy metal (P = 0.01). The LF/HF ratio on the other hand decreased during auditory stimulation with classical baroque music (P = 0.019). Acute auditory stimulation with the selected heavy metal musical auditory stimulation decreased the sympathetic and parasympathetic modulation on the heart, while exposure to a selected classical baroque music reduced sympathetic regulation on the heart.

Toll-like receptor 4 contributes to blood pressure regulation and vascular contraction in spontaneously hypertensive rats

Activation of TLRs (Toll-like receptors) induces gene expression of proteins involved in the immune system response. TLR4 has been implicated in the development and progression of CVDs (cardiovascular diseases). Innate and adaptive immunity contribute to hypertension-associated end-organ damage, although the mechanism by which this occurs remains unclear. In the present study, we hypothesize that inhibition of TLR4 decreases BP (blood pressure) and improves vascular contractility in resistance arteries from SHR (spontaneously hypertensive rats). TLR4 protein expression in mesenteric resistance arteries was higher in 15-week-old SHR than in age-matched Wistar controls or in 5-week-old SHR. To decrease the activation of TLR4, 15-week-old SHR and Wistar rats were treated with anti-TLR4 (anti-TLR4 antibody) or non-specific IgG control antibody for 15 days (1 mu g per day, intraperitoneal). Treatment with anti-TLR4 decreased MAP (mean arterial pressure) as well as TLR4 protein expression in mesenteric resistance arteries and IL-6 (interleukin 6) serum levels from SHR when compared with SHR treated with IgG. No changes in these parameters were found in treated Wistar control rats. Mesenteric resistance arteries from anti-TLR4-treated SHR exhibited decreased maximal contractile response to NA (noradrenaline) compared with IgG-treated SHR. Inhibition of COX (cyclo-oxygenase)-1 and COX-2, enzymes related to inflammatory pathways, decreased NA responses only in mesenteric resistance arteries of SHR treated with IgG. COX-2 expression and TXA(2) (thromboxane A(2)) release were decreased in SHR treated with anti-TLR4 compared with IgG-treated SHR. Our results suggest that TLR4 activation contributes to increased BP, low-grade inflammation and plays a role in the augmented vascular contractility displayed by SHR.

Oxidized low-density lipoproteins and their antibodies: Relationships with the reverse cholesterol transport and carotid atherosclerosis in adults without cardiovascular diseases

Background: Metabolic predictors and the atherogenicity of oxidized LDL (oxLDL) and the specific antibodies against oxLDL (oxLDL Ab) are unclear and controversial. Methods: In 107 adults without atherosclerotic manifestations, we measured oxLDL and oxLDL Ab, and also the activities of CETP. PLTP, lipases and the carotid intima-media thickness (cIMT). Comparisons were performed for the studied parameters between the lowest and the highest tertile of oxLDL and oxLDL Ab, and the relationships between studied variables were evaluated. Results: Subjects with higher oxLDL Ab present reduced hepatic lipase activity and borderline increased cIMT. In the highest oxLDL tertile, besides the higher levels of total cholesterol, LDL-C and apoB100, we found reduced CETP activity and higher cIMT. A significant correlation between oxLDL Ab and cIMT, independent of oxLDL, and a borderline correlation between oxLDL and cIMT independent of oxLDL Ab were found. In the multivariate analysis, apoAl was a significant predictor of oxLDL Ab, in contrast to regulation of oxLDL by apoB100, PLTP and inverse of CETP. Conclusions: In adults without atherosclerotic disease, the metabolic regulation and carotid atherosclerosis of oxLDLAb and oxLDL groups, characterized a dual trait in oxLDL Ab, as a contributor to carotid atherosclerosis, much less so than oxidized LDL, and with a modest atheroprotective role. (C) 2012 Elsevier B.V. All rights reserved.

The cardiovascular actions of fractalkine/CX3CL1 in the hypothalamic paraventricular nucleus are attenuated in rats with heart failure

The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the regulation of sympathetic nerve activity, which is significantly elevated in chronic heart failure (CHF). Fractalkine (FKN) and its cognate receptor, CX3CR1, are constitutively expressed in the central nervous system, but their role and physiological significance are not well known. The aims of the present study were to determine whether FKN plays a cardiovascular role within the PVN and to investigate how the actions of FKN might be altered in CHF. We show that both FKN and CX3CR1 are expressed on neurons in the PVN of rats, suggesting that they may have a physiological function in this brain nucleus. Unilateral microinjection of FKN directly into the PVN of anaesthetized rats elicited a significant dose-related decrease in blood pressure (1.0 nmol, -5 ± 3 mmHg; 2.5 nmol, -13 ± 2 mmHg; 5.0 nmol, -22 ± 3 mmHg; and 7.5 nmol, -32 ± 3 mmHg) and a concomitant increase in heart rate (1.0 nmol, 6 ± 3 beats min(-1); 2.5 nmol, 11 ± 3 beats min(-1); 5 nmol, 18 ± 4 beats min(-1); and 7.5 nmol, 27 ± 5 beats min(-1)) compared with control saline microinjections. In order to determine whether FKN signalling is altered in rats with CHF, we first performed quantitative RT-PCR and Western blot analysis and followed these experiments with functional studies in rats with CHF and sham-operated control rats. We found a significant increase in CX3CR1 mRNA and protein expression, as determined by quantitative RT-PCR and Western blot analysis, respectively, in the PVN of rats with CHF compared with sham-operated control rats. We also found that the blood pressure effects of FKN (2.5 nmol in 50 nl) were significantly attenuated in rats with CHF (change in mean arterial pressure, -6 ± 3 mmHg) compared with sham-operated control rats (change in mean arterial pressure, -16 ± 6 mmHg). These data suggest that FKN and its receptor, CX3CR1, modulate cardiovascular function at the level of the PVN and that the actions of FKN within this nucleus are altered in heart failure