Name: THAÍS DE ANDRADE JACINTO
Publication date: 16/12/2016
Advisor:
Name |
Role |
|---|---|
| SILVANA DOS SANTOS MEYRELLES | Advisor * |
Examining board:
| Name |
Role |
|---|---|
| SILVANA DOS SANTOS MEYRELLES | Advisor * |
| MARCELO PERIM BALDO | Internal Examiner * |
| FABIANA DAYSE MAGALHAES SIMAN MEIRA | External Examiner * |
Summary: Arterial hypertension is a multifactorial clinical condition characterized by elevated and sustained high levels of blood pressure, which is also associated with functional/structural changes in target organs such as heart, brain, kidneys and blood vessels and in the metabolic changes that increase risk of fatal and nonfatal cardiovascular disorders. The classic model of renovascular hypertension, 2 Kidney1 Clip (2K1C), was developed by Goldblatt in 1934. This model showed a substantial increase in blood pressure of dogs and has served for subsequent studies in renovascular hypertension. Reactive oxygen species (ROS) play important physiological role and are involved in diverse cellular functions such as defense against pathogens, gene expression, senescence, apoptosis, and regulation of cell growth. Our laboratory has shown that the renovascular hypertension accounts with the development of high levels of oxidative stress, resulting from ROSincreased production or decreased degradation.It is well known that stem cells have an important rolein tissue maintenance and homeostasis and can be affected by high levels of ROS. The entire hematopoietic system is generated from hematopoietic stem cells (HSCs) that has a long lifespan and a high potential for self-renewal. The focus of the present investigation is on the Sildenafil, which is a vasoactive drug commonlyused in the treatment of erectile dysfunction and pulmonary hypertension. It is a potent and selective inhibitor of phosphodiesterase type 5 (PDE5). The aim of this study was to evaluate the effect of sildenafil treatment on intracytoplasmic production of ROS in hematopoietic stem cells of mice with renovascular hypertension. Renovascular hypertension was induced by placing a steel clip around the left renal artery of male mice (C57BL/6) weighing between 23-23.5g. Two weeks after the induction of hypertension, the animals were randomly divided into two groups: treated with sildenafil (40 mg/kg/day (VIAGRA Pfizer, Sao Paulo, Brazil), orally (Sil, n=10) or vehicle (2K1C, n=10) for 2 weeks and compared with the control group (Sham, n=10). At the end of treatment, animals were euthanized, the kidneys and hearts were removed and weightedfor relative heart/tibia measurement. HSCs were isolated from bone marrow from femurs and tibiae. Cells was identified, quantified and intracytoplasmic production of free radicals, apoptosis and cycle cell were made.Data were expressed as mean±SEM. Statistical analysis was performed by one-way ANOVA followed by Tukeypost hoc test. Resultsshowed that 2K1C animals had an increase in superoxide anion production and the treatment with sildenafil prevented this increase (Sham 3805±237 vs. 2R1C 6562±456* vs.Sil 4447±395#&). The high levels of hydrogen peroxide, also decreased with treatment(Sham 3805±237 vs. 2R1C 6562±456* vs.Sil 4447±395#&).The same occurred with the highly reactive species of oxygen that were also decreased with treatment(Sham 1653±303 vs. 2R1C 2529±196* vs.Sil 1611±252#). The number of cells present in the bone marrow has dropped significantly in hypertensive animals, this situation was prevented with sildenafiltreatment (Sham 4,5 x 106±1,1 vs. 2R1C 2,4 x 106±0,7* vs.Sil 6,3 x 106±1,7#). Thesildenafil treatment also significantly decreased the number of HSCs with apoptosiswhen compared to control group, increasing the number of viable cells (Sham 59,3%±7,8 vs. 2R1C 46,7%±6* vs.Sil 80%±4,9#&).Considering the HSCs importance to body homeostasis and based on the data of the present study, we suggest sildenafil as an option to treatment of damaged HSCs observed in renovascular hypertension.
