A key system for cardiovascular control is click here the Renin Angiotensin System (RAS). It is well recognized that the RAS is susceptible to modulation by estrogen [7]. Clinical [39] and [48] and animal [25], [37] and [53] studies have indicated an inverse association between estrogen and the activation of the RAS. Increases in the circulating levels of ANG II and dysregulation (upregulation or activation) of the vasoconstrictor arm of the RAS have been implicated in many CVDs, including coronary artery disease (CAD). Several studies have suggested that estrogen has modulatory effects on angiotensin II receptors expression, as the decrease in the expression of AT1 receptor in various organs [14] and [37].

Conversely, Baiardi et al. have shown that estrogen causes an upregulation of both ANG II receptors in female rat kidneys [4]. Moreover, estrogen can modify other compounds of the RAS, such as circulating angiotensinogen [11] and [48], plasma renin activity [5] and [59] or concentration [8], serum angiotensin-converting enzyme (ACE) activity [5] and [8], ANG I [5], ANG II [8], or plasma and tissue ACE activity [5], [8], [14] and [18]. Another risk factor for developing CVD is the increase in adipose tissue. Estrogen has been recognized as an important regulator

of female adipose tissue development and deposition in humans, rodents and other species [31]. After menopause, estrogen insufficiency is thought to be largely responsible for the redistribution of fat to the upper body [19]. In addition, there are reports showing that estrogen deficiency decreases lipolysis in adipose tissue [13]. On the other hand, the estrogen replacement

therapy prevents the central medroxyprogesterone MAPK Inhibitor Library chemical structure fat distribution [19] as well as decreases fatty acid synthesis and increases the lipolysis rate [23], which indicates a direct action of estrogen in fat cells. Numerous epidemiological studies have convincingly shown that physical exercise has a beneficial effect on cardiovascular disease outcomes. Exercise reduces heart rate and blood pressure, augments myocardial oxygen uptake, and regulates circulating blood volume as well as various metabolic processes. According to reports of the consistent benefits of regular physical exercise to the general population [2], a systematic review of randomized controlled trials reported benefits of exercise on metabolic and cardiovascular parameters in post-menopausal women [3]. However, although most studies have investigated the role of exercise in the condition of estrogen deficiency, such as occurs in menopause, few studies have reported the role of physical exercise on the RAS in the cardiovascular system. In a study conducted by Habouzit et al., female rats were submitted to chronic running training, and no changes in the activity of plasma or muscle ACE were found [20]. Another study showed that the involvement of the RAS in left ventricular hypertrophy was induced by swimming training in female rats [40].