These results suggest that combined therapy using B and I is more effective than therapy with either drug at monotherapy for controlling renal damage in this animal model. In addition, data presented here reaffirm the benefit of interacting against renin-angiotensin-system (RAS) in the metabolic syndrome.

Objective: To determine whether angiotensin converting enzyme inhibition by perindopril can reduce cardiac transforming growth factor b1 (TGFb1) and plasminogen activator inhibitor 1 (PAI-1) and therefore control collagen accumulation in an animal model with the metabolic syndrome such as the obese Zucker rat (OZR). Animals: Male OZR (group 1, n = 10); OZR treated with perindopril (group 2, n = 10); and lean Zucker rats (group 3, n = 10). Methods: During six months, group 2 received 3 mg/kg/day of perindopril orally and group 1 and group 3 were given a vehicle. Hearts were processed for pathology studies including immunohistochemical analysis with antibodies to PAI-1, TGFb1, collagen type I, and collagen type III. Results: Group 2 had lower blood pressure (126.7 (2) v 148.6 (2.7) mm Hg, p , 0.01) than untreated OZR and had decreased cardiac PAI-1 (3.6 (0.4) v 13.5 (1.7)% of positive area/field, p , 0.01), TGFb1 in myocytes (0.13 (0.1) v 9.14 (4.7)%/area, p , 0.01) and in interstitium (19.8 (6.8) v 178.9 (27.4) positive cells/area, p , 0.01), collagen I (3 (0.8) v 13.3 (1)%/area, p , 0.01), collagen III (5 (0.6) v 9.5 (0.9)%/area, p , 0.01), and collagen I to collagen III ratio (0.59 (0.13) v 1.40 (0.15) p , 0.01) compared with untreated OZR. Conclusion: These results suggest that perindopril reduces cardiac PAI-1 and TGFb1 and ameliorates cardiac fibrosis in a rat model with multiple cardiovascular risk factors.T he association of obesity, non-insulin dependent diabetes mellitus, and arterial hypertension constitutes the well known metabolic syndrome X, which is deeply involved in the development of cardiovascular disease with deleterious consequences.1 In addition, cardiac fibrosis, one of the major factors in the development of heart failure, is highly prevalent in all the aforementioned diseases.Accumulated information supports the notion that angiotensin II has, independently of its hypertensive effect, an essential role in cardiac fibrogenesis by itself and through its action on transforming growth factor b1 (TGFb1) and plasminogen activator inhibitor 1 (PAI-1).2 3 Angiotensin II induces TGFb1, a multifunctional profibrogenic cytokine that regulates cell differentiation of fibroblast into myofibroblast.4 5 Both fibroblast and, especially, myofibroblast regulate fibrogenesis in the heart by producing collagen in the cardiac interstitium. Interestingly, cardiac myofibroblasts express requisite components of the renin-angiotensin system, including angiotensinogen, renin, and angiotensin converting enzyme (ACE), and can generate angiotensin II de novo.6 7 Moreover, angiotensin II can also induce PAI-1, which inhibits activation not only of plasminogen but also of plasmin matrix metalloproteinases (collagenases), which are involved in collagen degradation.8 Consequently, increased PAI-1 concentration either in plasma or in tissue can reduce extracellular matrix degradation, contributes to the accumulation of interstitial collagen, and leads to impaired function of the fibrinolytic system. Therefore, thrombotic e...

These results suggest that LDC of PER + IND can control cardiovascular damage in OZR providing an additional help in the metabolic scenario likewise.