Comparative antihypertensive and renoprotective effects of telmisartan and lisinopril after long-term treatment in hypertensive diabetic rats

Abstract

This study compared the cardiovascular and renal effects of long-term telmisartan (3 and 10 mg/kg/day)and lisinopril (10 mg/kg/day) in an animal model combining hypertension and diabetes mellitus. It was a parallel-group study of diabetic, spontaneously hypertensive rats (SHR), treated with control or active treatment for eight months. A non-diabetic SHR control group was run in parallel. Diabetes was induced by streptozotocin (45 mg/kg i.v.) in SHRs aged 9-10 weeks. Animals were treated with telmisartan (3 or 10mg/kg/day), lisinopril (10 mg/kg/day) or vehicle. Plasma glucose levels, blood pressure (BP), and urinary protein and albumin excretion were measured monthly. Telmisartan treatment significantly reduced BP of diabetic SHRs in a dose-dependent manner (p<0.05, low-dose, n= 18; p<0.01, high-dose, n=15). The BP reduction in the lisinopril group was similar to that in the telmisartan 10 mg/kg/day group. Compared with non-diabetic SHRs, untreated diabetic SHRs developed severe proteinuria and albuminuria over the experimental period (p<0.01). In diabetic SHRs, proteinuria and albuminuria were dose-dependently and significantly attenuated by treatment with telmisartan (p<0.01 with the higher dose) and lisinopril (p<0.01). Compared with the untreated diabetic SHRs, cardiac hypertrophy was significantly reduced after treatment with both doses of telmisartan and with lisinopril. Telmisartan, 10 mg/kg/day, but not lisinopril, significantly attenuated the diabetes-induced increase in glomerular volume. In conclusion, telmisartan, 10 mg/kg/day, is at least as beneficial as lisinopril, 10 mg/kg/day, in lowering BP, reducing cardiac hypertrophy and attenuating renal excretion of protein and albumin in this model.

Effect of telmisartan on expression of protein kinase C-? in kidneys of diabetic mice

“…Immunohistochemistry Immunofluorescence staining and confocal laser scanning microscopy were performed as previously described [21] . All steps were performed at room temperature.…”

“…Experimental and clinical studies have established that blocking the rennin Ang system (RAS) reduces the glomerular filtration of proteins and delays the deterioration of renal function in DN [20,21] . However, the molecule events that underlie the impact of RAS remain unclear.…”

Renoprotective effects of telmisartan in the 5/6 nephrectomised rats

“…In addition, telmisartan also showed renoprotective effects in some animal models: spontaneously hypertensive rats (SHR), 10 as well as the hypertensive diabetic model that combines SHR with streptozotocininduced diabetes. 11 Ohmura et al 12 investigated the mechanism of the renoprotective effect of telmisartan using obese Zucker diabetic rats. Ciclosporin A-induced nephropathy in pigs was attenuated by telmisartan without any reduction of blood pressure (BP).…”

Freehand three-dimensional echocardiographic evaluation of the effect of telmisartan compared with hydrochlorothiazide on left ventricular mass in hypertensive patients with mild-to-moderate hypertension: a multicentre study

“…10 Other distinguishing features of telmisartan are its almost exclusive biliary excretion and terminal elimination half-life of about 24 h. 11 Clinical studies have shown the ability of once-daily telmisartan to provide effective control of blood pressure. 11 Preclinical studies suggest that telmisartan is highly effective in reducing LVH, [12][13][14][15] and preliminary observations provide evidence for the clinical efficacy of telmisartan in the treatment of LVH at doses that confer effective blood pressure control. 16,17 The purpose of the present study was to compare the effect of the standard therapeutic dose of telmisartan 80 mg with that of the thiazide diuretic hydrochlorothiazide (HCTZ) 25 mg on blood pressure, LVM and tolerability in hypertensive subjects after 12 months of treatment.…”