Ivabradine treatment lowers blood pressure and promotes cardiac and renal protection in spontaneously hypertensive rats.

Hypertension is linked to hyperpolarization-activated cyclic nucleotide-gated (HCN) function, expressed in excitable and non-excitable cells. Considering that the reduction in heart rate (HR) improves coronary perfusion and cardiac performance, ivabradine (IVA) emerged as an important drug for the treatment of cardiovascular diseases. AIM: Evaluate if IVA chronic treatment effect can mitigate hypertension and reverse the cardiac and renal damage in SHR. MAIN METHODS: Rats were divided into 4 groups treated for 14 days with PBS (1 ml/kg; i.p) or IVA (1 mg/kg; i.p): 1) WKY PBS; 2) SHR PBS; 3) WKY IVA; and 4) SHR IVA. The systolic blood pressure (SBP) was measured, indirectly, before and during the treatment period with IVA (day 0, 1, 7 and 11). Rats were subjected to artery cannulation for direct blood pressure (BP) measurement. Morphofunctional and gene expression were evaluated in the heart and kidneys. KEY FINDINGS: IVA reduced SBP only in SHR on the 7th day. Direct blood pressure measurement showed that IVA chronic treatment reduced HR in the SHR. Interestingly, mean arterial pressure (MAP) was reduced in SHR IVA when compared to SHR PBS. Serum and urinary biochemical data were not altered by IVA. Moreover, IVA reduced the renal inflammatory infiltrates and increased glomerular density, besides preventing the cardiac inflammatory and hypertrophic responses. SIGNIFICANCE: IVA treatment lowered blood pressure, improved cardiac remodeling and inflammation, as well as decreasing renal damage in SHR. Further, IVA increased renal HCN2 mRNA and reduced cardiac HCN4 mRNA.

Early ovarian hormone deprivation increases cardiac contractility in old female rats-Role of physical training.

OBJECTIVES: We investigated the effects of early ovarian hormones deprivation on morphology and cardiac function and the effects of aerobic training on these parameters, in old rats. METHODS: Female Wistar rats (N = 48) were divided into two groups, at 10 weeks of life: early ovarian hormones deprivation by ovariectomy (OVX; N = 24) and sham (SHAM; N = 24). Between weeks 62 and 82, 12 animals of each group underwent aerobic training (OVX-T and SHAM-T, N = 12). At the end of week 82, all were evaluated by echocardiography, cardiac function (Langendorff technique) and cardiac ß-adrenergic receptor expression quantification. RESULTS: Echocardiography showed slight changes in morphology between OVX and SHAM groups. OVX group (Δ = 101 ±â€¯4.7 mmHg) showed higher values for maximal left intraventricular pressure in response to dobutamine, when compared to SHAM group (Δ = 55 ±â€¯11.8 mmHg). Both OVX-T (Δ = 70 ±â€¯4.0 mmHg) and SHAM-T (Δ = 22 ±â€¯6.6 mmHg) groups showed a reduction in this response. While, ß-adrenergic receptor expression was not different between the untrained groups, SHAM-T (0.23 ±â€¯0.02 AU) and OVX-T (0.29 ±â€¯0.01 AU), showed decreased expression of these receptors. CONCLUSION: Early ovarian hormones deprivation associated with aging, promotes discrete changes in cardiac morphology and increasing cardiac contractility. Aerobic training decreases ß-adrenergic receptors expression, influencing the cardiac contractility.

Diet associated with exercise improves baroreflex control of sympathetic nerve activity in metabolic syndrome and sleep apnea patients.

PURPOSE: We tested the hypothesis that (i) diet associated with exercise would improve arterial baroreflex (ABR) control in metabolic syndrome (MetS) patients with and without obstructive sleep apnea (OSA) and (ii) the effects of this intervention would be more pronounced in patients with OSA. METHODS: Forty-six MetS patients without (noOSA) and with OSA (apnea-hypopnea index, AHI > 15 events/h) were allocated to no treatment (control, C) or hypocaloric diet (- 500 kcal/day) associated with exercise (40 min, bicycle exercise, 3 times/week) for 4 months (treatment, T), resulting in four groups: noOSA-C (n = 10), OSA-C (n = 12), noOSA-T (n = 13), and OSA-T (n = 11). Muscle sympathetic nerve activity (MSNA), beat-to-beat BP, and spontaneous arterial baroreflex function of MSNA (ABRMSNA, gain and time delay) were assessed at study entry and end. RESULTS: No significant changes occurred in C groups. In contrast, treatment in both patients with and without OSA led to a significant decrease in weight (P < 0.05) and the number of MetS factors (P = 0.03). AHI declined only in the OSA-T group (31 ± 5 to 17 ± 4 events/h, P < 0.05). Systolic BP decreased in both treatment groups, and diastolic BP decreased significantly only in the noOSA-T group. Treatment decreased MSNA in both groups. Compared with baseline, ABRMSNA gain increased in both OSA-T (13 ± 1 vs. 24 ± 2 a.u./mmHg, P = 0.01) and noOSA-T (27 ± 3 vs. 37 ± 3 a.u./mmHg, P = 0.03) groups. The time delay of ABRMSNA was reduced only in the OSA-T group (4.1 ± 0.2 s vs. 2.8 ± 0.3 s, P = 0.04). CONCLUSIONS: Diet associated with exercise improves baroreflex control of sympathetic nerve activity and MetS components in patients with MetS regardless of OSA.

Therapy With Mesenchymal Stem Cells in Parkinson Disease: History and Perspectives.

BACKGROUND: Parkinson disease (PD) is a neurodegenerative disorder affecting the basal nuclei, causing motor and cognitive disorders. Bearing in mind that standard treatments are ineffective in delaying the disease progression, alternative treatments capable of eliminating symptoms and reversing the clinical condition have been sought. Possible alternative treatments include cell therapy, especially with the use of mesenchymal stem cells (MSC). REVIEW SUMMARY: MSC are adult stem cells which have demonstrated remarkable therapeutic power in parkinsonian animals due to their differentiation competence, migratory capacity and the production of bioactive molecules. This review aims to analyze the main studies involving MSC and PD in more than a decade of studies, addressing their different methodologies and common characteristics, as well as suggesting perspectives on the application of MSC in PD. CONCLUSIONS: The results of MSC therapy in animal models and some clinical trials suggest that such cellular therapy may slow the progression of PD and promote neuroregeneration. However, further research is needed to address the limitations of an eventual clinical application.

Heart rate variability in chronic Chagas patients before and after treatment with benznidazole.

BACKGROUND: There is no consensus regarding large-scale use of benznidazole to treat Chagas disease, because of its toxicity and low efficacy during the chronic phase. OBJECTIVES: To evaluate heart rate variability in chronic Chagas patients before and after treatment with benznidazole. METHODS: Twenty-one Chagas patients with positive blood cultures and/or PCR received benznidazole (5 mg/kg twice daily for 60 days) and were matched for age and gender with 24 Chagas individuals with negative blood cultures, as controls. R-R intervals were assessed in time and frequency domains using an autoregressive algorithm under three different conditions: baseline, cold face and active tilt tests. Power spectral densities in low and high-frequency bands were estimated in absolute and normalized units. Data were expressed as mean±SD or medians (lower and upper quartiles). Groups were compared using non-paired or paired Student's T, Mann-Whitney or Wilcoxon tests, as required. The significance level was 5%. RESULTS: The groups were comparable regarding age, gender and clinical disease forms. There were no differences in temporal and spectral indices between groups in baseline and cold face tests. Treated patients presented significantly lower tachycardic responses in mean R-R intervals during the active tilt test (p=0.0200) than controls did. Genetic characterization of T. cruzi isolates from treated group samples showed that 100% belonged to genotype II. CONCLUSION: For the first time in the medical literature, we detected sympathetic impairment during the active tilt test in chronic Chagas patients treated with benznidazole. This finding may be partially explained by benznidazole neurotoxicity.

Increased cardiac sympathetic drive and reduced vagal modulation following endothelin receptor antagonism in healthy conscious rats.

1. The present study evaluated changes in autonomic control of the cardiovascular system in conscious rats following blockade of endothelin (ET) receptors with bosentan. 2. Rats were treated with bosentan or vehicle (5% gum arabic) for 7 days by gavage. 3. Baseline heart rate (HR) was higher in the bosentan-treated group compared with the control group (418 +/- 5 vs 357 +/- 4 b.p.m., respectively; P < 0.001). This baseline tachycardia was associated with a lower baroreflex sensitivity of the bradycardiac and tachycardiac responses in the bosentan-treated group compared with the control group. Sequential blockade of the parasympathetic and sympathetic autonomic nervous system with methylatropine and propranolol showed a higher intrinsic HR in the bosentan-treated group compared with the control group (411 +/- 5 vs 381 +/- 4 b.p.m., respectively; P < 0.05). This was accompanied by a higher cardiac sympathetic tone (31 +/- 1 vs 13 +/- 1%, respectively; P < 0.01) and a lower vagal parasympathetic tone (69 +/- 2 vs 87 +/- 2%, respectively; P < 0.01) in the bosentan-treated group compared with the control group. Variance and high-frequency oscillations of pulse interval (PI) variability in absolute and normalized units were lower in the bosentan-treated group than in the control group. Conversely, low-frequency (LF) oscillations of PI variability in absolute and normalized units, as well as variance and LF oscillations of systolic arterial pressure variability, were greater in the bosentan-treated group than the control group. 4. Overall, the data indicate an increased cardiac sympathetic drive, as well as lower vagal parasympathetic activity and baroreflex sensitivity, in conscious rats after chronic blockade of ET receptors with bosentan.