Renovascular hypertension increases serum TNF and CX3CL1 in experimental Trypanosoma cruzi infection.

Trypanosoma cruzi triggers a progressive inflammatory response affecting cardiovascular functions in humans and experimental models. Angiotensin II, a key effector of the renin-angiotensin system, plays roles in mediating hypertension, heart failure, and inflammatory responses. T. cruzi and AngII can induce inflammatory responses by releasing inflammatory mediators. The aim of this study was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats infected with T. cruzi. Our data showed an increase in serum AngII in uninfected and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham) animals. The baseline systolic blood pressure was higher in both uninfected and infected 2K1C rats. Despite no difference in circulating parasites in the acute phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post-infection in 2K1C rats in association with higher cardiac inflammatory infiltration. In summary, AngII-induced hypertension associated with T. cruzi infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat model, thereby intensifying cardiac inflammatory infiltration and worsening the underlying inflammation triggered by this protozoan.

Influence of ßS-Globin Haplotypes and Hydroxyurea on Arginase I Levels in Sickle Cell Disease.

Introduction. Sickle cell disease (SCD) is characterized by hemoglobin S homozygosity, leading to hemolysis and vasoocclusion. The hemolysis releases arginase I, an enzyme that decreases the bioavailability of nitric oxide, worsening the symptoms. The different SCD haplotypes are related to clinical symptoms and varied hemoglobin F (HbF) concentration. The aim of this study was to evaluate the impact of the ßS gene haplotypes and HbF concentration on arginase I levels in SCD patients. Methods. Fifty SCD adult patients were enrolled in the study and 20 blood donors composed the control group. Arginase I was measured by ELISA. The ßS haplotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analyses were performed with GraphPad Prism program and the significance level was p < 0.05. Results. Significant increase was observed in the arginase I levels in SCD patients compared to the control group (p < 0.0001). The comparison between the levels of arginase I in three haplotypes groups showed a difference between the Bantu/Bantu × Bantu/Benin groups; Bantu/Bantu × Benin/Benin, independent of HU dosage. An inverse correlation with the arginase I levels and HbF concentration was observed. Conclusion. The results support the hypothesis that arginase I is associated with HbF concentration, also measured indirectly by the association with haplotypes.

Cardiac and renal effects induced by different exercise workloads in renovascular hypertensive rats

We examined the effect of exercise training (Ex) without (Ex 0 percent) or with a 3 percent workload (Ex 3 percent) on different cardiac and renal parameters in renovascular hypertensive (2K1C) male Fisher rats weighing 150-200 g. Ex was performed for 5 weeks, 1 h/day, 5 days/week. Ex 0 percent or Ex 3 percent induced similar attenuation of baseline mean arterial pressure (MAP, 119 ± 5 mmHg in 2K1C Ex 0 percent, N = 6, and 118 ± 5 mmHg in 2K1C Ex 3 percent, N = 11, vs 99 ± 4 mmHg in sham sedentary (Sham Sed) controls, N = 10) and heart rate (HR, bpm) (383 ± 13 in 2K1C Ex 0 percent, N = 6, and 390 ± 14 in 2K1C Ex 3 percent, N = 11 vs 371 ± 11 in Sham Sed, N = 10,). Ex 0 percent, but not Ex 3 percent, improved baroreflex bradycardia (0.26 ± 0.06 ms/mmHg, N = 6, vs 0.09 ± 0.03 ms/mmHg in 2K1C Sed, N = 11). Morphometric evaluation suggested concentric left ventricle hypertrophy in sedentary 2K1C rats. Ex 0 percent prevented concentric cardiac hypertrophy, increased cardiomyocyte diameter and decreased cardiac vasculature thickness in 2K1C rats. In contrast, in 2K1C, Ex 3 percent reduced the concentric remodeling and prevented the increase in cardiac vasculature wall thickness, decreased the cardiomyocyte diameter and increased collagen deposition. Renal morphometric analysis showed that Ex 3 percent induced an increase in vasculature wall thickness and collagen deposition in the left kidney of 2K1C rats. These data suggest that Ex 0 percent has more beneficial effects than Ex 3 percent in renovascular hypertensive rats.

Cardiac and renal effects induced by different exercise workloads in renovascular hypertensive rats.

We examined the effect of exercise training (Ex) without (Ex 0%) or with a 3% workload (Ex 3%) on different cardiac and renal parameters in renovascular hypertensive (2K1C) male Fisher rats weighing 150-200 g. Ex was performed for 5 weeks, 1 h/day, 5 days/week. Ex 0% or Ex 3% induced similar attenuation of baseline mean arterial pressure (MAP, 119 ± 5 mmHg in 2K1C Ex 0%, N = 6, and 118 ± 5 mmHg in 2K1C Ex 3%, N = 11, vs 99 ± 4 mmHg in sham sedentary (Sham Sed) controls, N = 10) and heart rate (HR, bpm) (383 ± 13 in 2K1C Ex 0%, N = 6, and 390 ± 14 in 2K1C Ex 3%, N = 11 vs 371 ± 11 in Sham Sed, N = 10,). Ex 0%, but not Ex 3%, improved baroreflex bradycardia (0.26 ± 0.06 ms/mmHg, N = 6, vs 0.09 ± 0.03 ms/mmHg in 2K1C Sed, N = 11). Morphometric evaluation suggested concentric left ventricle hypertrophy in sedentary 2K1C rats. Ex 0% prevented concentric cardiac hypertrophy, increased cardiomyocyte diameter and decreased cardiac vasculature thickness in 2K1C rats. In contrast, in 2K1C, Ex 3% reduced the concentric remodeling and prevented the increase in cardiac vasculature wall thickness, decreased the cardiomyocyte diameter and increased collagen deposition. Renal morphometric analysis showed that Ex 3% induced an increase in vasculature wall thickness and collagen deposition in the left kidney of 2K1C rats. These data suggest that Ex 0% has more beneficial effects than Ex 3% in renovascular hypertensive rats.

Evidence for a role of AT(2) receptors at the CVLM in the cardiovascular changes induced by low-intensity physical activity in renovascular hypertensive rats.

In the present study, we evaluated the involvement of the rennin-angiotensin system (RAS) in the control of the blood pressure (BP), baroreceptor-mediated bradycardia and the reactivity of caudal ventrolateral medulla (CVLM) neurons to Ang II and to AT(2) receptor antagonist in sedentary or trained renovascular hypertensive rats. Physical activity did not significantly change the baseline mean arterial pressure (MAP), heart rate (HR) or the sensitivity of the baroreflex bradycardia in normotensive Sham rats. However, in 2K1C hypertensive rats, physical activity induced a significant fall in baseline MAP and HR and produced an improvement of the baroreflex function (bradycardic component). The microinjections of Ang II into the CVLM produced similar decreases in MAP in all groups, Sham and 2K1C, sedentary and trained rats. The hypotensive effect of Ang II at the CVLM was blocked by previous microinjection of the AT(2) receptors antagonist, PD123319, in all groups of rats. Unexpectedly, microinjection of PD123319 at the CVLM produced a depressor effect in 2K1C sedentary that was attenuated in 2K1C trained rats. No significant changes in MAP were observed after PD123319 in Sham rats, sedentary or trained. These data showed that low-intensity physical activity is effective in lowering blood pressure and restoring the sensitivity of the baroreflex bradycardia, however these cardiovascular effects are not accompanied by changes in the responsiveness to Ang II at CVLM in normotensive or hypertensive, 2K1C rats. In addition, the blood pressure changes observed after AT(2) blockade in 2K1C rats suggest that hypertension may trigger an imbalance of AT(1)/AT(2) receptors at the CVLM that may be restored, at least in part, by low-intensity physical activity.

Atherosclerosis and acute arterial thrombosis in rabbits: a model using balloon desendothelization without dietary intervention.

Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1% cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80%) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P < 0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.

Atherosclerosis and acute arterial thrombosis in rabbits: a model using ballon desendothelization without dietary intervention

Acute thrombosis can be induced in rabbits by a triggering protocol using Russell's viper venom and histamine given after 8 months of a 1 per cent cholesterol diet and balloon desendothelization. In the present study, we tested the hypothesis that aortic desendothelization performed 4 months before the triggering protocol without a high cholesterol diet is a highly effective and less expensive way of producing arterial atherosclerosis and thrombosis. Nineteen male New Zealand white rabbits on a normal diet were studied. The control group (N = 9) received no intervention during the 4-month observation period, while the other group (N = 10) was submitted to aortic balloon desendothelization using a 4F Fogarty catheter. At the end of this period, all animals were killed 48 h after receiving the first dose of the triggering treatment. Eight of 10 rabbits (80 per cent) in the balloon-trauma group presented platelet-rich arterial thrombosis while none of the animals in the control group had thrombus formation (P<0.01). Thus, this model, using balloon desendothelization without dietary manipulation, induces arterial atherosclerosis and thrombosis and may provide possibilities to test new therapeutic approaches.

Site of entry of kininase II into renal tubular fluid.

The stop-flow technique was used to determine the site of entry of kininase II into tubular fluid in dogs. Stop-flow patterns were constructed for kininase II, p-aminohippurate, sodium, and potassium. The proximal tubule was localized by the peak of p-aminohippurate concentration and the distal tubule by the minimum sodium concentration. In the stop-flow pattern for kininase II, three peaks (a, b, and c) were observed. A main peak (a), located 2.25 +/- 0.45 ml distal to the p-aminohippurate peak (p less than 0.01) and 3.75 +/- 0.31 ml proximal to the minimum sodium concentration (p less than 0.001), was observed in all experiments. Peak c, located 2.6 +/- 0.4 ml (p less than 0.01) proximal to the p-aminohippurate peak, was observed in five dogs. Peak b appeared in five dogs and was always located 2.0 ml distal to the minimum sodium concentration. This peak was coincident with the potassium peak. Only two of eight experiments showed all three peaks. These results showed that the major kininase II entry into the tubular fluid is near the p-aminohippurate peak and that distal entry occurred in 63% of the dogs.