Estudo do papel do Sry no sistema cardiovascular e sua interação com o sistema renina angiotensina

Abstract

The systemic arterial hypertension (SAH) is a multifactorial, polygenetic and sexlinked medical condition characterized by high and sustained levels of blood pressure (BP). One of the components of the complex network that regulates PA is the renin angiotensin system (RAS), which influences the homeostasis of salt and water and vascular tone, has been extensively studied in correlation with hypertension and cardiovascular disease. The SRA can be basically divided into a vasoconstrictor axis (ACE/ANG II/AT1) and a vasodilator axis (ACE2/ANG 17/MAS/AT2) directly correlated to regulation via the MAP kinases: ERK 1/2, JNK and p38. Many studies show that there is a higher incidence of hypertension and CVD in men compared to women. Recently, studies have demonstrated the involvement of the Sry locus on the Y chromosome in the interaction with the SRA of rats. The aim of this study was to analyze the role of human Sry gene in the regulation of blood pressure and renin angiotensin system of mice strains Sprangue Dawley (SD); and evaluate in primary culture of neonatal rat cardiomyocytes SD and Wistar its interaction with the renin angiotensin system. Sprangue Dawley rats were subjected to the techniques of electroporation and transfection by renal carbon nanotubes multi-walled (NTCPM) for delivery of clones containing Sryh (P Sryh ) and Sry3 (P Sry3 ) via carotid and were monitored by telemetry for blood pressure. The viability was checked by transfection of light and transmission electron microscopy. From the transfection of Sryh , Sry3, siSry and siMas, functionalized with NTCPM, there was a relationship of Sry to the following: regulation of blood pressure, heart rate, gene expression of RAS, expression of t y r o sin e h y d r o x yla s e and ERK1 / 2, JNK and p38. The results obtained by microscopy confirmed the transfection and telemetry showed a significant increase in blood pressure and heart rate of the animals transfected with Sry3 and Sryh when compared to controls, similar to the data obtained by the technique of kidney electroporation. After transfection into cardiomyocytes of SD and Wistar rats with Sryh , there was a significant increase in the expression of the of renin , ACE , AT2 , TH , JNK and ERK 1/2 but decrease in the expression of p38; without significant changes to AT1, ACE2 and MAS . We also observed by flow cytometry, an increase in the size and granularity of cardiomyocytes after treatment, which were confirmed by HE and immunofluorescence techniques. These data suggest the involvement of Sry in hypertrophy mechanism. By inhibiting the expression of the genes Sry and MAs by siRNA technique, there is a regulatory effect on Sry receptor but probably via the inhibition of MAP kinases, JNK and ERK 1/2. However, Sry3 produced a significant increase in blood pressure of SD rats in the same way reported in the literature for Wistar Kyoto, showing that Sry has physiological actions conserved in the studied strains of R a tt u s n o r v e gic u s . The Sryh regulates blood pressure, interferes with gene expression of the vasoconstrictor via the SRA, and the precursor pathway of catecholamines from the increased expression of tyrosine hydroxylase. The latter probably due to increased expression of AT2 receptor.