Angiotensin (1-7), small but complicated, needs more exercise.

Ang (1-7) is generated by angiotensin-converting enzyme 2 (ACE2) from AngII,6 and has many protective effects on the cardiovascular system through its receptor.7 Shah and colleagues8 used 2-kidney 1-clip (2K1C) hypertensive rats and assigned them to either a sedentary or trained group. Chronic infusion of Ang (1-7) attenuated hypertension and cardiac hypertrophy only in the trained rats, but not in the sedentary rats. In ventricular tissue, the Mas receptor and the angiotensin type 2 receptor (AT2R), both putative Ang (1-7) receptors,7 were more upregulated in the trained 2K1C rats than the sedentary 2K1C rats. They also showed that the levels of phosphorylated endothelial nitric oxide synthase (p-eNOS) was highest in the ventricular tissue of trained 2K1C rats after Ang (1-7) infusion. Costa and colleagues revealed that acute infusion of Ang (1-7) to SHR diminished mean arterial pressure and the antihypertensive effect of Ang (1-7) was blocked by a NOS inhibitor, L-NAME.9 Ang (1-7) increased eNOS, p-eNOS, and NOS activities in the ventricles of SHR. The in vitro study using ventricular slices showed Ang (1-7)-induced NOS activity was blocked by an AT2R antagonist and bradykinin B2 receptor antagonist, but not by the Mas receptor antagonist. Putative receptors of Ang (1-7) are controversial. Santos argued about the specificity of the AT2R antagonist,7 and Xu t is generally accepted that exercise training reduces the risk of cardiovascular diseases (CVD), but the precise mechanisms for this reduction are not fully understood. Mora and colleagues followed up 27,055 women for 11 years and found the risk factors investigated in their study explained 59% of the physical activity-related reduction in CVD.1 Green and colleagues thought that this result suggests at least 40% of the risk reduction by exercise cannot be explained by traditional risk factors and they proposed direct effects of exercise on the vascular wall and attributed it to improvement of endothelial function by shear forces (Figure 1).2