COMPARATIVE PATHOLOGY

Author: CHAMORRO MARÍN VIRGINIA.
Year: 2004.
University: GRANADA.
Place of defense: FACULTAD DE MEDICINA - UNIVERSIDAD DE GRANADA.
Place of preparation: INSTITUTO DE NEUROCIENCIAS, FACULTAD DE MEDICINA - UNIVERSIDAD DE GRANADA.

Summary: Although the plasma renin activity (APR) and plasma levels of anglotensina II (Ang II) do not increase in spontaneously hypertensive rats (SHR), there is considerable evidence suggesting that the renin-angiotensin system (MRS) plays an important role in the pathogenesis of this experimental model. Thus, the chronic blockade of receptor AT1 attenuates development of hypertension, renal damage and cardiac hypertrophy in the SHR. The classical view of the Ang II as a vasoactive agent involved in the local and systemic hemodynamic regulation has been expanded recently to see it as a real cytokine. It has long been known that the Ang II tissue plays a role in cardiac hypertrophy and renal damage in hypertension. The Endothelin (ET) also participates as a growth factor in the hipertrofía cardiac fibrosis and renal pathology hypertensive. The SHR model is characterized by an increase in oxidative stress. In fact, the reduction of superoxide anions with superoxide dismutase CuZn (SOD) lowers blood pressure in SHR. In addition, the administration tempol, a Mimetic of SOD, also lowers blood pressure (BP) in the SHR. The Ang II can contribute to the maintenance of hypertension through stimulation of oxidative stress. In addition, Ang II can increase the production of ET which has also been shown that stimulates oxidative stress. These changes combined with a reduction of nitric oxide (NO), which is sequestered by the superoxide ion, could potentiate the effect vasoconstructor of Ang II and thus able to explain how hypertension is maintained when the levels of Ang II are normal. Thus, it has been proposed that this sequence of events may play a role in the pathophysiology of SHR. Chronic administration of deoxicorticosterona (DOCA) in hypertensive rats deficit ON, increases the PA abolishes the APR and makes this type of hypertension is resistant receptor blockade AT1. In the model DOCA-sal, chronic administration of antagonists AT1 not reduce the PA, but improves hipertrofía cardiac and renal damage. The mineral corticoids (MF) are classically hormones that retain sodium, although recently it has been found that are modular in function and cardiovascular damage. The MF, despite dela retention of water and salt, they show an increase in the concentration of intracellular sodium, reduce exchange Na + -Ca2 +, and open channels of calcium (Ca2 +) voltage dependent on the vascular smooth muscle. This leads to an elevation in the concentration of calciointracelular, which increases the contractility of fibers actomiosina. The MC, also have several harmful effects on the cardiovascular system, including myocardial necrosis and fibrosis, hardening and vascular damage, a decrease of fibrinolysis, release of catecholamines (CT) and producing cardiac arrhythmias. Vascular level, the MC are involved in hypertrophy and hyperplasia of vascular smooth muscle cells, as well as the deterioration of the matrix and vascular endothelial dysfunction. Despite the impact prohipertensos listed on the MC, treatment with DOCA without supplementation with salt, the PA does not increase as originally described Selye in years 40 and confirmed by other more recent studies. However, we know that adding the DOCA SHR rats or rats treated with a non-specific inhibitor ON (L-NAME) produced a greater increase in the PA. Many studies show that losartán reduces blood pressure administered acutely or chronically SHR, but has a minimal effect on the rats treated with salt normotensive or hypertension DOCA-sal. However, there are few studies which examine the effect of losartán on renal haemodynamics and excretion of sodium and water. Similarly, nor is it known whether the administration crónic 8 to the DOC d90 A, which raises blood pressure in SHR and not in WKY controls, produces these changes in renal haemodynamics PA altering or management of renal sodium and water in a different way controls and SHR. Against this background, we have the following objectives: 1-Analyze the involvement of oxidative stress and tissue ET Ang II and on the effects of the blockade receptor AT1 sobrela PA, hipetrofia cardiac and renal damage in rats SHR, and analyze how those effects modified when hypertension is spontaneously transformed into a model of low renin by the administration of DOCA. 2-To assess the contribution of potential functional changes in vessel resistance to further increase the PA produced by chronic administration of the DOCA SHR rats. 3-Finally, this study explores the effects of acute blockade of the SRA with losartán on renal haemodynamics and renal function in SHR rats and DOCA-treated SHR their respective controls and to try to determine whether these factors involved in the action presora the DOCA in SHR. The following conclusions were as follows: 1 - Chronic administration of deoxicorticosterona (DOCA) aggravates hypertension, ventricular hypertrophy and renal damage in SHR rats. These animals also have an increase of oxidative stress and levels of ET in the renal cortex, changes that could contribute to the damage caused by the DOCA hypertension in SHR. 2 - The losartán reduces oxidative stress in rats SHR regardless of the state of the plasma renin activity and produces a significant reduction in Ang II and ET kidney and urinary ET in SHR rats treated with DOCA, which can participate in effect renoprotector of this drug. 3, Ang-II ventricular seems not participate in the increase in ventricular hypertrophy in DOCA-treated rats, which could be due to the increased PA rats and a hypertrophic and fibrótico direct effect of MEC. 4, DOCA-PS increases in the SHR but no increases the curve flujo-presión or renal vascular reactivity to vasoconstrictors, and does not reduce the vasodilatory response to endothelium-dependent and independent of the SHR rat or WKY. Therefore, the elevation of PA inducing DOCA in SHR can not be explained by changes in vascular reactivity in vessels of resistance. 5 - The study of the hemodynamic and renal function after an acute saline expansion in SHR rats and DOCA-treated SHR, demonstrate that chronic administration of DOCA not manifest greater sodium retention or greater increase in vascular resistance renal SHR rats that justifies the effect presor the DOCA in these animals.