Table 2.

Summary of recent clinical research on renin–angiotensin system

Author	Results/Interpretations
Bojestig et al 2000	PRA and Ang II concentrations were significantly lower in diabetic patients than in the controls. The levels of atrial natriuretic peptide, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA(1c) during the previous five years.
Brenner et al 2001 for the RENAAL Study	Losartan reduced the incidence of a doubling of the serum creatinine concentration (risk reduction, 25%; P = 0.006) and end-stage renal disease (risk reduction, 28%; P = 0.002) but had no effect on the rate of death. Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy.
Dahlof et al 2002	Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated. Losartan seems to confer benefits beyond reduction in blood pressure, and new onset diabetes was less frequent with losartan.
Gross et al 2007	The survey of specific functional polymorphisms of the RAS, namely the angiotensin-I-converting enzyme (ACE) D/I, the angiotensinogen (AGT) T174M and M235T, and A1166C of the angiotensin-II receptor 1 (AGTR1), revealed that the incidence recurrent instent restenosis in a high risk cohort was not associated with any of the polymorphisms examined in this study.
Gumprecht et al 2000	The results of this study suggest that ACE gene insertion/deletion and angiotensinogen M235T polymorphisms contribute to the increased risk for the development of chronic renal failure,
HOPE 2000	Ramipril was beneficial for cardiovascular events and overt nephropathy in people with diabetes. The cardiovascular benefit was shown to be greater than that attributable to the decrease in blood pressure.
Lieb et al 2006	This study provides evidence that genetic variants in the ACE2 gene may be associated with left ventricular mass, septal wall thickness, and left ventricular hypertrophy in hemizygous men.
Lewis et al 2001	The angiotensin-II-receptor blocker irbesartan was effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection was independent of the reduction in blood pressure it causes.
Lindholm et al 2002	Losartan was more effective than atenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes, and left ventricular hypertrophy. Losartan seems to have benefits beyond blood pressure reduction.
Matayoshi et al 2007	This study shows that the systemic RAS may modulate insulin sensitivity in essential hypertensive patients.
Merrill et al 2002	This study demonstrates, for the first time, increased plasma Ang-(1–7) in normal pregnant subjects compared with nonpregnant subjects and decreased Ang-(1–7) in preeclamptic subjects compared with normal pregnant subjects.
Mukai et al 2002	The results of this study demonstrate that long-term inhibition of the renin-angiotensin system of COX-2-derived vasoconstricting factors and superoxide anions.
Nogueira et al 2007	This study suggests that reduced levels of the vasodilator Ang-(1–7) could be implicated in the endothelial dysfunction seen in gestational diabetic women during and after pregnancy.
Parving et al 2001	This study showed that Irbesartan is renoprotective independently of its blood-pressure-lowering effect in patients with type 2 diabetes and microalbuminuria
Simões e Silva et al 2006b	This study showed different circulating RAS profiles between hypertensive and in normotensive chronic renal failure subjects. Marked changes in plasma Ang-(1–7) were associated with the presence of hypertension and progression of kidney dysfunction.
Simões e Silva et al 2004	This study showed different RAS profiles in childhood hypertension and suggested a blood pressure-independent change of Ang-(1–7) in essential hypertension.
Wijpkema et al 2006	In this study, the authors could establish a role for the AT1R 1166A/C polymorphism in restenosis after percutaneous coronary intervention. However, significant gene – gene interaction was suggested for the ACE gene and the HO-1 promotor, meriting further investigation in restenosis.
Winkelmann et al 1999	The significant relations observed in this study between the AGT M235T variant, its protein product, and the cardiovascular disease phenotypes provide evidence for a possible role of elevated circulating angiotensinogen in the pathogenesis of coronary artery disease.
Yang et al 2007	The results of this study indicate that common genetic variants in the ACE2 gene might impact on myocardial infarction in females, and may possibly interact with alcohol consumption to affect the risk of coronary heart disease and myocardial infarction in Chinese males.
Yusuf et al 2001	This study demonstrated that ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals.
Zhong et al 2006	This study concluded that the ACE2 A/G polymorphism is associated with hypertension in patients with metabolic syndrome.
Zisman et al 2003	This study showed that Ang-(1–7)-forming activity from both Ang I and Ang II was increased in failing human heart ventricles but it was mediated by at least two different angiotensinases. The first, which demonstrated substrate preference for Ang I, was neutral endopeptidase-like. The second was ACE2, as demonstrated by Western blotting and inhibition of activity with C16.