Abstract
The present study investigated the effects of telmisartan, a selective AT1 receptor antagonist, on renal function in dogs. Conscious female dogs were treated with (i) vehicle (controls) and three doses of telmisartan (0.03 mg/kg, 0.1 mg/kg and 0.3 mg/kg) administered intravenously; (ii) vehicle and three doses of telmisartan (0.3 mg/kg, 1.0 mg/kg and 3.0 mg/kg) administered orally; or (iii) 1.0 mg/kg per day telmisartan orally for 12 days. Eight dogs were used for each experiment. Each of the four treatments in (i) and (ii) was administered 7 days apart. During the 6 h after intravenous administration, urine volume was significantly higher in dogs treated with telmisartan 0.1 mg/kg (8.5 ± 1.6 ml/kg) and 0.3 mg/kg (7.0 ± 0.9 ml/kg) than controls (2.7 ± 0.3 ml/kg; P < 0.05), and renal sodium excretion was increased significantly with telmisartan 0.03 mg/kg (803 ± 124 μmol/kg), 0.1 mg/kg (1039 ± 213 μmol/kg) and 0.3 mg/kg (966 ± 161 μmol/kg) versus controls (159 ± 21 μmol/kg; P < 0.05). Oral telmisartan at doses of 1.0 mg/kg and 3.0 mg/kg also produced significant increases in urine volume (7.2 ± 1.1 ml/kg and 6.6 ± 1.2 ml/kg, respectively) and renal sodium excretion (599 ± 146 μmol/kg and 555 ± 131 μmol/kg, respectively) compared with controls (2.8 ± 0.5 ml/kg and 80 ± 33 μmol/kg; P < 0.05) over the 6-h post-dose period. Telmisartan at all intravenous doses and at 3.0 mg/kg orally increased the urinary excretion of chloride significantly over the 6-h post-dose period compared with vehicle alone. The excretion of potassium and creatinine were unchanged by any treatment. Telmisartan 1.0 mg/kg administered orally for 12 days produced similar results. In conclusion, acute intravenous or oral as well as subchronic oral administration of telmisartan to conscious dogs promotes diuresis and natriuresis without affecting potassium or creatinine excretion.