Effects of amlodipine orotate on hypertension-related complications in spontaneously hypertensive rats.

Hypertension is a common problem in elderly patients, which usually requires chronic therapy under various physiological conditions including low gastric acidity (hypo- or anacidity). This study investigated a new salt type of amlodipine (CAS 88150-42-9) on blood pressure and hypertension-related complications in stroke-prone spontaneously hypertensive rats (SHR-SP). Amlodipine orotate was prepared by reacting orotic acid and amlodipine to increase the dissolution rate at higher gastric pH conditions. Twelve-week-old SHR-SP were randomly divided into five groups to receive either amlodipine orotate or amlodipine besylate (CAS 111470-99-6) at the doses of 3 and 10 mg/kg/day orally for four weeks. The age-matched normotensive Wistar Kyoto rats (WKY) served as the normal positive control group. The systolic blood pressure was reduced in the amlodipine treated SHR-SP in a dose-dependent manner with a similar potency irrespective of the salt type. Both amlodipines also reduced the left ventricular hypertrophy at high doses and concentration-dependently inhibited the Ca 2+ induced contraction with a similar potency. Furthermore, semi-quantitative analysis of a cerebral injury revealed that the two salts of amlodipine reduced the stroke-related lesions to a similar degree. These results suggest that the amlodipine orotate is effective in terms of its effects on hypertension, cardiac hypertrophy and stroke-related cerebral damage in SHR-SP.