Synergism of Telmisartan and Amlodipine on Blood Pressure Reduction and Cardiorenal Protection in Hypertensive Rats

• DOI: 10.1097/fjc.0b013e3182073e41
• Publication Date: 2011-01-26T04:57:54Z
• Authors: Wei Liu; Wei Wang; Shu-Wei Song; Xiao-Fei Gu; Xiu-Juan Ma; Feng-Yun Su; Hao Zhang; Ai-Jun Liu; Ding-Feng Su
• Keywords: Male; Cardiotonic Agents; Dose-Response Relationship, Drug; Kidney Glomerulus; Angiotensin-Converting Enzyme Inhibitors; Blood Pressure; Drug Synergism; Calcium Channel Blockers; Kidney; Benzoates; Rats; 3. Good health; Disease Models, Animal; 03 medical and health sciences; 0302 clinical medicine; Rats, Inbred SHR; Hypertension; Animals; Benzimidazoles; Drug Therapy, Combination; Kidney Diseases; Amlodipine; Antihypertensive Agents

This study was designed to investigate the effects of telmisartan and amlodipine on reduction of blood pressure (BP), myocardial hypertrophy, and renal injury in hypertensive rats.In acute experiments, the BP was measured in conscious freely moving rats. Spontaneously hypertensive rats were treated with intragastric administration of amlodipine (1, 2, 4 mg/kg), telmisartan (4, 8, 12, 16, 20 mg/kg), and their different combinations (4 + 4, 2 + 4, 4 + 8, 4 + 12, 1 + 4, 2 + 8, 4 + 16, 2 + 12, 1 + 8, 2 + 16, 2 + 20, 1 + 12, 1 + 16, 1 + 20 mg/kg). The probability sum test (q test) was used to evaluate the synergistic action on BP reduction. In two-kidney, one-clip rats, the effects of amlodipine (1 mg/kg), telmisartan (6 mg/kg) and their combination on BP reduction were observed. In the chronic study, spontaneously hypertensive rats were treated with amlodipine (1 mg/kg), telmisartan (6 mg/kg), and their combination for 4 months. Histopathologic examinations were performed after the determination of BP and BP variability.There is a synergistic interaction between amlodipine and telmisartan on BP reduction. The optimal dose ratio was found at 1:6. The synergistic effect of this dose ratio (1:6) was also seen in two-kidney, one-clip rats. Long-term treatment with this combination results in a beneficial effect on the reduction of BP and BP variability. The end-organ damage, including myocardial hypertrophy, glomerular atrophy, and fibrosis, was significantly attenuated by this combination.The optimal dose ratio of amlodipine and telmisartan on BP was 1:6. This combination is beneficial for the BP and BP variability reduction and end-organ damage prevention.