Qual o melhor bloqueio do sistema renina angiotensina aldosterona na hipertensão? / Renin-angiotensin aldosterone system: what is the best blockade?

Os fármacos que inibem a hiperatividade do sistema reninaangiotensina- aldosterona (SRAA) estão entre os mais importantes agentes anti-hipertensivos devido à sua eficácia sobre o controle dos níveis tensionais e redução de eventos cardiovasculares. Três são as classes de anti-hipertensivos com ação primariamente inibitória do SRAA: os inibidores da enzima conversora de angiotensina (IECA), os bloqueadores dos receptores de angiotensina (BRA) e os inibidores diretos da renina (IDR). Apesar da eficácia anti-hipertensiva destas três classes ser relativamente semelhante, as evidências diferem quanto à capacidade sobre a redução dos eventos cardiovasculares que cada uma proporciona. A proposta deste artigo é comparar as evidências quanto à eficácia e segurança das três classes de fármacos inibidores do SRAA, buscando possibilitar uma escolha consciente e crítica na prática clínica.

Drugs that inhibit the hyperactivity of the reninangiotensin- aldosterone system (RAAS) are among the most important antihypertensive agents due to their effectiveness on the control of blood pressure and reducing cardiovascular events. There are three classes of antihypertensive which primarily action is RAAS inhibition: angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blocker (ARB) and direct renin inhibitors (IDR). Although the antihypertensive efficacy of these three classes is relatively similar, evidence differ in their ability on reduction of cardiovascular events. The purpose of this article is to compare the evidence regarding the efficacy and safety of the three classes of drugs that inhibit the RAAS, seeking to enable a conscious and critical choice in clinical practice.

Renovascular Hypertension and Nephrotic Range Proteinuria Developed after the Renal Artery Ligation: Successful Treatment by Combination of ACE Inhibitor and Angiotensin II Type 1 Receptor Blocker / 대한신장학회지

A 27-year-old woman presented with severe hypertension and nephrotic range proteinuria. She had a blunt renal trauma 4 weeks ago and was treated by the left main renal artery ligation. The plasma renin activity, angiotension II and aldosterone levels were very high and the abdominal angiography showed the occlusion of the left main renal artery with relatively preserved blood flow in upper pole of the left kidney. In captopril renal scan, relatively preserved perfusion in upper pole of left kidney was further compromised after captopril administration. The massive proteinuria and hypertension were improved after combination of ACE inhibitor and angiotensin II type 1 receptor blocker treatment.

Inhibitory Effect of Angiotensin Blockade on Hepatic Fibrosis in Common Bile Duct-ligated Rats / 대한간학회지

BACKGROUNDS AND AIMS: Angiotensin receptors are found on hepatic stellate cells, which participate in hepatic fibrosis. Therefore, it is presumed that angiotensin has a role in hepatic fibrosis. The aim of this study was to evaluate the effects of angiotensin blockade on inhibition of hepatic fibrosis in cirrhotic rat model. Material and METHODS: Cirrhosis with portal hypertension was produced by common bile duct ligation (BDL) in the adult Sprague-Dawley rats. They were classified into 4 groups (each group n=6) as follows; G1: BDL without drug, G2: BDL+captopril 100 mg/kg/day beginning 2 weeks after BDL, G3: BDL+captopril 100 mg/kg/day, starting just after BDL, G4: BDL+losartan 10 mg/kg/day, starting just after BDL. After 4 weeks following BDL, hepatic fibrosis was histomorphologically analyzed by Batts & Ludwig score. Alpha smooth muscle actin by immunohistochemical stain, hydroxyproline contents of liver tissue by spectrophotometry and expression of collagen, procollagen, and TGF-beta by real-time PCR were measured. RESULTS: Batts & Ludwig score were 3.8, 3.0, 2.6,and 2.6 in G1, G2, G3, and G4, respectively. The expression of alpha-SMA was significantly lower in G3 and G4 than in G1; 11.9%, 10.9%, 2.6%, and 1.1% in G1, G2, G3, and G4, respectively (p<0.05). The concentration of hydroxyproline (microgram/g liver tissue) was lower in G3 and G4 compared with G1 (p<0.05). Also, the administration of angiotensin blockade just after BDL significantly reduced the expression of collagen, procollagen, and TGF-beta mRNA. CONCLUSIONS: Angiotensin blockades are effective in the prevention of hepatic fibrosis in BDL rats.

The Additive Beneficial Effects of Ramipril Combined with Candesartan in Hypertensive Patients on Insulin Resistance, Plasma Adiponectin

BACKGROUND AND OBJECTIVES: Ramipril and candesartan have decreased the incidence of new onset diabetes in large scale randomized clinical studies. Because ramipril and candesartan have distinct mechanisms of action in the renin angiotensin aldosterone system, we hypothesized that combination therapy would have additive beneficial metabolic effects in patients with hypertension. SUBJECTS AND METHODS: Thirty-four patients were given ramipril 10 mg and placebo, ramipril 10 mg and candesartan 16 mg, or candesartan 16 mg and placebo daily in a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms and two washout periods (each being 2 months). RESULTS: Ramipril, combination therapy or candesartan significantly increased the plasma adiponectin levels relative to the baseline measurements by 17+/-6% (p=0.038), 25+/-5% (p<0.001), and 14+/-6% (p=0.016), respectively. Combination therapy significantly increased the plasma adiponectin levels more than either ramipril or candesartan alone (p=0.020 by ANOVA). Only combination therapy significantly increased the QUICKI level relative to the baseline measurements (p=0.002). There were no significant correlations between these changes of the metabolic parameters and reduction of the systolic blood pressure (-0.288< or =r< or =0.284) and reduction of the diastolic blood pressure (-0.282< or =r< or =0.190). On multivariate analysis, only the change of adiponectin levels was an independent predictor of the changes in the QUICKI levels (beta=1.549, p=0.040) following combination therapy. CONCLUSION: Ramipril in combination with candesartan increases the plasma adiponectin levels to a greater extent than monotherapy with either drug alone. Only combination therapy significantly improves insulin sensitivity relative to the baseline measurements. The only predictor for the improvement of insulin sensitivity is the increase of plasma adiponectin levels by combination therapy.