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 Ca2+ induced contraction with a similar potency. Furthermore, semi-quantitative analysis of a cerebral injury revealed that the two salts of amlodipine reduced the stroke-re-lated 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.
Choi
Seul Min
SM
Research Laboratories, Dong-A Pharmaceutical Company, Kyunggi-do, Korea.
Kim
Jee Eun
JE
Ahn
Byoung Ok
BO
Kwon
Jong Won
JW
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009963:Orotic Acid / Q000627:therapeutic use*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D017311:Amlodipine; D009963:Orotic Acid; D002118:Calcium