Acute renal denervation normalizes aortic function and decreases blood pressure in spontaneously hypertensive rats.

Mechanisms involved in the acute responses to renal denervation (RDN) have yet to be fully understood. We assessed urinary volume, autonomic control and aorta vascular reactivity after acute RDN. Male normotensive Wistar rats and spontaneously hypertensive rats (SHR) were divided into normotensive + RDN (ND) or sham surgery (NS), and hypertensive + RDN (HD) or sham surgery (HS). Metabolic parameters and hemodynamic measurements were recorded 72h and 4 days after intervention, respectively. Aortic rings were studied 7 days post RDN in an isometric myograph. Concentration-response curves to phenylephrine, sodium nitroprusside and acetylcholine (10-10-10-5 M) were performed. Two-way ANOVA was used for group comparisons and differences reported when p < 0.05. Results are presented as mean ± SEM. Urinary volume was 112% higher in HD vs. HS (HS = 14.94 ± 2.5 mL; HD = 31.69 ± 2.2 mL) and remained unchanged in normotensive rats. Systolic BP was lower in HD rats (HS = 201 ± 12 vs. HD = 172 ± 3 mmHg) without changes in normotensive group. HD group showed increased HF and LF modulation (HS = 5.8 ± 0.7 ms2 vs. HD = 13.4 ± 1.4 ms2; HS = 3.5 ± 0.7 ms2 vs. HD = 10.5 ± 1.7 ms2, respectively). RDN normalized vascular reactivity in HD rats and increased phenylephrine response in ND rats. Acute fall in BP induced by RDN is associated with increased urinary volume, which in turn may also have contributed to functional changes of the aorta.

(Pro)renin receptor expression in myocardial infarction in transgenic mice expressing rat tonin.

The (pro)renin receptor [(P)RR] has been implicated as a renin/prorenin receptor, and plays a role in local renin angiotensin system activation. Our goal was to investigate whether a transgenic mouse that expresses rat tonin [TGM'(rTon)] can regulate (P)RR mRNA levels. Control (C) and TGM'(rTon) animals were subdivided into the C sham, C MI, TGM'(rTon) sham, and TGM'(rTon) MI groups. The levels of tonin, (P)RR, and renin were determined using RT-PCR mRNA. Tonin activity as determined by RIE was significantly increased in the TGM'(rTon) sham group as compared to the C sham group in the atrium (AT) and right ventricle (RV), respectively. In most mice, tonin mRNA levels were significantly reduced compared to those in the TGM'(rTon) sham group in the atria. In this structure, the (P)RR mRNA levels were statistically significantly reduced in the TGM'(rTon) sham and TGM'(rTon) MI groups compared to the control groups. However, the (P)RR mRNA values were significantly increased when we compared the TGM'(rTon) MI vs TGM'(rTon) sham groups. In the RV, the renin mRNA levels in the TGM'(rTon) sham group were significantly reduced compared to the C sham group. Tonin overexpression may act in the regulation of (P)RR mRNA levels during MI.

Erratum: Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice.

[This corrects the article on p. 257 in vol. 13, PMID: 28702435.].

Interval and continuous aerobic exercise training similarly increase cardiac function and autonomic modulation in infarcted mice.

The present study aimed to compare the effects of moderate-intensity continuous and high-intensity interval exercise training (ET) on exercise tolerance, cardiac morphometry and function, hemodynamic, and cardiac autonomic modulation in myocardial infarcted mice. Wild-type mice (WT) were divided into four groups: sedentary WT (S); WT myocardium infarction sedentary (IS); WT myocardium infarction underwent to moderate-intensity continuous ET (MICT), and WT myocardium infarction underwent to high-intensity interval ET (MIIT). After 60 days of descending coronary artery ligation, moderate-intensity continuous ET consisted of running at 60% of maximum, while the high-intensity interval training consisted of eight sprints of 4 min at 80% of maximum and a 4-min recovery at 40% of maximum. Both exercises were performed 1 hr a day, 5 days a week, during 8 weeks. Results demonstrated that IS showed elevated exercise tolerance, as well as decreased hemodynamic and heart function, and autonomic control. On the other hand, both programs of ET were equally effective to increase all parameters, without further differences between the groups. In conclusion, the results of the present study showed that myocardial infarction leads to damage in both investigated strains and the two types of physical exercise attenuated the major impairments provoked by myocardial infarction in exercise tolerance, cardiac structure, cardiac function, hemodynamic and cardiac autonomic modulation.

Resveratrol and grape juice differentially ameliorate cardiovascular autonomic modulation in L-NAME-treated rats.

Polyphenols consumption detected in red wine and grape juice may prevent or help in the treatment of hypertension. However, cardiovascular autonomic effects of polyphenols were poorly studied. Therefore, we evaluated the effects of resveratrol and grape juice treatments in hemodynamics, baroreflex sensitivity, heart rate (HR) and blood pressure (BP) variability and cardiac redox parameters. Male Wistar rats were divided in 3 groups (n=7/each) and treated for 30 days: only L-NAME-treated (60 mg/kg/day by oral gavage), L-NAME+resveratrol (L-NAME+R) and L-NAME+grape juice (L-NAME+G). BP signal was directly recorded and pulse interval (PI) and systolic arterial pressure (SAP) variability were analyzed in time and frequency domains. Baroreflex sensitivity (BRS) was determined by the alpha index. Oxidized and reduced glutathione concentrations were determined in cardiac tissue. L-NAME increased BP with no differences among groups (mean BP: L-NAME=124±4, L-NAME+R=126±3 and L-NAME+G=125±4 mmHg). PI and SAP variability expressed by total variance were also similar among groups. However, normalized low frequency (LF) and high frequency (HF) components of PI variability were lower and higher, respectively, in both R and G-treated groups when compared to only L-NAME group. Interestingly, sympathetic modulation to the vessels (LF from SAP variability) and BRS were decreased and increased, respectively, only in L-NAME+R rats. Additionally, GSH/GSSG ratios were higher in L-NAME+R and L-NAME+G than in L-NAME group. Our results indicate that resveratrol and grape juice treatments can modulate autonomic function and promote cardiac redox benefits even when nitric oxide is decreased. Moreover, resveratrol influences not only cardiac but also vascular autonomic modulation.

Preventive role of exercise training in autonomic, hemodynamic, and metabolic parameters in rats under high risk of metabolic syndrome development.

High fructose consumption contributes to metabolic syndrome incidence, whereas exercise training promotes several beneficial adaptations. In this study, we demonstrated the preventive role of exercise training in the metabolic syndrome derangements in a rat model. Wistar rats receiving fructose overload in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) or kept sedentary (F) for 10 wk. Control rats treated with normal water were also submitted to exercise training (CT) or sedentarism (C). Metabolic evaluations consisted of the Lee index and glycemia and insulin tolerance test (kITT). Blood pressure (BP) was directly measured, whereas heart rate (HR) and BP variabilities were evaluated in time and frequency domains. Renal sympathetic nerve activity was also recorded. F rats presented significant alterations compared with all the other groups in insulin resistance (in mg · dl(-1) · min(-1): F: 3.4 ± 0.2; C: 4.7 ± 0.2; CT: 5.0 ± 0.5 FT: 4.6 ± 0.4), mean BP (in mmHG: F: 117 ± 2; C: 100 ± 2; CT: 98 ± 2; FT: 105 ± 2), and Lee index (in g/mm: F = 0.31 ± 0.001; C = 0.29 ± 0.001; CT = 0.27 ± 0.002; FT = 0.28 ± 0.002), confirming the metabolic syndrome diagnosis. Exercise training blunted all these derangements. Additionally, FS group presented autonomic dysfunction in relation to the others, as seen by an ≈ 50% decrease in baroreflex sensitivity and 24% in HR variability, and increases in sympathovagal balance (140%) and in renal sympathetic nerve activity (45%). These impairments were not observed in FT group, as well as in C and CT. Correlation analysis showed that both Lee index and kITT were associated with vagal impairment caused by fructose. Therefore, exercise training plays a preventive role in both autonomic and hemodynamic alterations related to the excessive fructose consumption.

Walking promotes metabolic and baroreflex sensitivity improvement in fructose-fed male rats.

The aim of this study was to investigate metabolic and cardiovascular responses to walking in fructose-fed rats. Male Wistar rats were divided into control (C), sedentary fructose (SF) and walking fructose (WF). Fructose-fed rats received D-fructose (100 g/l). WF rats walked on a treadmill at constant load (0.3 km/h) during 1 h/day, 5 days/week for 8 weeks. Measurements of triglyceride concentrations, adipose tissue and glycemia were carried out together with insulin tolerance test to evaluate metabolic profile. Arterial pressure (AP) signals were directly recorded. Baroreflex sensitivity (BR) was evaluated by the reflex tachycardia (TR) and bradycardia (BR) to AP changes. The results showed that walking decreased the adipose tissue (SF: 6.5 ± 0.4; WF: 2.8 ± 0.1; C: 3.0 ± 0.3 g), blood triglyceride levels (SF: 291 ± 6.5; WF: 150 ± 8.1; C: 103 ± 4.5 mg/dl) and increased insulin sensitivity (SF: 2.5 ± 0.2; WF: 3.3 ± 0.32; C: 4.8 ± 0.4 %/min). Baroreflex sensitivity was improved in the WF group expressed by BR (SF: 0.75 ± 0.10; WF: 1.18 ± 0.10; C: 1.5 ± 0.14 ms/mmHg) and TR (SF: 0.80 ± 0.12; WF: 1.21 ± 0.10; C: 1.35 ± 0.11 ms/mmHg), as well as when verified by the alpha index. Although the WF group showed decreased AP when compared with the SF group, the values still enhanced in relation to C rats (SF: 137 ± 2; WF: 129 ± 1; C: 115 ± 6 mmHg). Our findings allow a better understanding of the effects of walking, a low-intensity exercise training, on the hemodynamic and metabolic aspects of male rats with metabolic syndrome and indicate that walking seems to be particularly effective in treating metabolic disturbances in this model.

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats.

OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 ± 0.2 vs. C: 4.5 ± 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 ± 3 vs. C: 104 ± 4 mmHg) and obesity (F: 0.31 ± 0.001 vs. C: 0.29 ± 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats

OBJECTIVE: High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations. METHODS: Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05. RESULTS: Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6 ± 0.2 vs. C: 4.5 ± 0.2 mg/dl/min), hypertension (mean blood pressure, F: 118 ± 3 vs. C: 104 ± 4 mmHg) and obesity (F: 0.31±0.001 vs. C: 0.29 ± 0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function. CONCLUSION: The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.

Baroreflex sensitivity impairment is associated with cardiac diastolic dysfunction in rats.

BACKGROUND: Studies have shown that the autonomic dysfunction accompanied by impaired baroreflex sensitivity was associated with higher mortality. However, the influence of decreased baroreflex sensitivity on cardiac function, especially in diastolic function, is not well understood. This study evaluated the morphofunctional changes associated with baroreflex impairment induced by chronic sinoaortic denervation (SAD). METHODS AND RESULTS: Animals were divided into sinoaortic denervation (SAD) and control (C) groups. Baroreflex sensitivity was evaluated by tachycardic and bradycardic responses, induced by vasoactive drugs. Cardiac function was studied by echocardiography and by left ventricle (LV) catheterization. LV collagen content and the expression of regulatory proteins involved in intracellular Ca(2+) homeostasis were quantified. Results showed higher LV mass in SAD versus C animals. Furthermore, an increase in deceleration time of E-wave in the SAD versus the C group (2.14 ± 0.07 ms vs 1.78 ± 0.03 ms) was observed. LV end-diastolic pressure was increased and the minimum dP/dt was decreased in the SAD versus the C group (12 ± 1.5 mm Hg vs 5.3 ± 0.2 mm Hg and 7,422 ± 201 vs 4,999 ± 345 mm Hg/s, respectively). SERCA/NCX ratio was lower in SAD than in control rats. The same was verified in SERCA/PLB ratio. CONCLUSIONS: The results suggest that baroreflex dysfunction is associated with cardiac diastolic dysfunction independently of the presence of other risk factors.