Impact of Telmisartan Versus Ramipril on Renal Endothelial Function in Patients With Hypertension and Type 2 Diabetes

Abstract

OBJECTIVE -One of the earliest signs of vascular change is endothelial dysfunction, which is also known to provoke albuminuria and to predict cardiovascular prognosis. The aim of this study was to analyze the effects of renin-angiotensin system (RAS) blockade on renal endothelial function.RESEARCH DESIGN AND METHODS -In a multicenter, prospective, double-blind, forced-titration, randomized study, 96 patients with type 2 diabetes, hypertension, glomerular filtration rate Ͼ80 ml/min, and normo-or microalbuminuria were treated once daily with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks. RESULTS -The mean, reflecting the magnitude of nitric oxide (NO) activity, increased with telmisartan from 71.9 Ϯ 9.0 ml/min before therapy to 105.2 Ϯ 9.7 ml/min at the end of treatment (P Ͻ 0.001). With ramipril, RPF response to L-NMMA increased from 60.1 Ϯ 12.2 to 87.8 Ϯ 9.2 ml/min (P ϭ 0.018). The adjusted difference between treatments was Ϫ17.1 Ϯ 13.7 ml/min (P ϭ 0.214). In accordance, telmisartan increased RPF at rest (i.e., without L-NMMA) from 652.0 Ϯ 27.0 to 696.1 Ϯ 31.0 ml/min (P ϭ 0.047), whereas ramipril produced no significant changes in RPF. The more the basal NO activity improved, the greater was the vasodilatory effect on renal vasculature (r ϭ 0.47, P Ͻ 0.001).CONCLUSIONS -In patients with type 2 diabetes, telmisartan and ramipril both increased NO activity of the renal endothelium significantly, which in turn may support the preservation of cardiovascular and renal function. Diabetes Care 30:1351-1356, 2007T he close link between cardiovascular and renal changes due to cardiovascular risk factors, such as arterial hypertension and diabetes, has stimulated increasing interest (1-3). Albuminuria and decreased renal function, which are both primarily known to predict renal outcome, have now been identified as excellent predictors of cardiovascular morbidity and mortality (2-4). Most surprisingly, their predictive power surpasses that of classic risk markers of cardiovascular and atherosclerotic disease (5). Albuminuria is related to intrarenal hydraulic pressure, podocyte function, electric charge, and increased permeability, provoked by endothelial dysfunction (6). Prospective studies have demonstrated the predictive value of endothelial dysfunction for future cardiovascular morbid events when assessed in the peripheral and coronary circulation (7-9) and most likely, although not yet proven, in the renal circulation.The endothelium is a major regulator of vascular homeostasis, with functional integrity being essential for the maintenance of blood flow and antithrombotic activity (10). Nitric oxide (NO), formed from L-arginine in the presence of NO synthase, is released by the vascular endothelial cells and brings about relaxation of vascular tissue and inhibition of platelet aggregation and adhesion (11). Endothelial dysfunction occurs as a result of impairment of NO synthesis or increased NO degradation and has been detected in patients with hypertension, peripheral arterial occlusive disease, and chronic re...

Effects of ACE-Inhibitors and Angiotensin Receptor Blockers on Inflammation

“…Only quinapril induced net change in the acetylcholineprovoked constriction of target segments of the coronaries after 6 months of treatment in a population formed of normotensive patients with coronary artery disease and without confounding variables such as heart failure, cardiomyopathy, or major lipid abnormalities. Similar results of improvement of flow-dependent endothelium-mediated vasodilation are reported in further two studies: the first, even in subjects affected by CAD, reported a similar extent of reduction after 4 weeks of therapy with ramipril 10 mg/d or losartan 100 mg/d through increase of bioavailability of NO [220]; the second, evaluated in renal circulation, after once daily treatment with 40/80 mg telmisartan or 5/10 mg ramipril for 9 weeks [221]. No significant differences between the two drugs were observed although the ARB seemed to be a little more efficient.…”

Angiotensin Receptor Blockers With Pleiotropic Properties: A New Standard in Cardiovascular Risk Management and Treatment of Hypertension

“…При этом только телмисартан достоверно снижал сосудистое сопротивление в почках, улучшал почечный кровоток в покое и достоверно повышал уровень ади-понектина -цитокина, выделяемого адипоцитами, улучшающего углеводный обмен [29].…”

“…Противовоспалительные эффекты PPAR-g за-ключаются в снижении выработки фактора роста фиб-робластов, молекул клеточной адгезии, воспалитель-ных цитокинов [31]. Активация PPAR-g улучшает функ-цию эндотелия [32], в том числе, у пациентов с СД и по-ражением почек [29]. Механизм действия широко…”

Angiotensin receptor blockers for the reduction of proteinuria in diabetic patients with overt nephropathy: results from the AMADEO study

“…16 The recently published Telmisartan versus Ramipril in renal Endothelial DYsfunction (TRENDY) study provided the fi rst head-to-head comparison of an ARB and an ACE inhibitor on renal endothelial function. 30 TRENDY was performed in 96 patients with type 2 diabetes who had mild-to-moderate hypertension (seated SBP/diastolic blood pressure [DBP] 140 to 180/90 to 110 mm Hg), normo-or microalbuminuria, and GFR Ͼ 80 mL/minute/1.73 m 2 . Patients were randomized to either telmisartan 40 mg or ramipril 5 mg for 3 weeks, followed by telmisartan 80 mg or ramipril 10 mg for 6 weeks.…”