The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the physiological regulation of blood pressure and in the pathophysiological disruption of cardiovascular organ damages. Angiotensin II (Ang II) is the primary biological mediator of the RAAS. Pathophysiological actions of Ang II is mediated by the angiotensin II type I receptor, for examples of vasoconstriction on vascular smooth muscle, secretion of aldosterone, reabsorption of sodium in the renal proximal nephron, and cell growth and proliferation.
Treatments of RAAS inhibitors, angiotensin converting enzyme and Ang II type I receptor antagonist, in hypertensive rat models caused prevention effects of hypertension, cardiac hypertrophy, and vascular sclerosis and glomerular sclerosis. In addition, these effects were associated with suppressive gene expressions of TGF-b, collagen type I, collagen type II, fibronectin. These gene expression were caused by the stimulation of Ang II type I receptor through the activation of mitogen-activated protein kinases (ERK and JNK). Both angiotensin converting enzyme and Ang II type I receptor antagonist inhibited the activation of ERK and JNK.