title: Alagebrium (ALT-711) improves the anti-hypertensive efficacy of nifedipine in diabetic-hypertensive rats.
abstract: Combining drugs with complementary mechanisms of action may contribute to improved hypertension control in diabetic patients. Advanced glycation end-product (AGE) breakers, a new class of candidate drugs targeting aging-related cardiovascular dysfunction, may be useful as novel adjuvant agents to improve the efficacy of diabetic hypertension (DH) treatment. This study evaluated the effects of alagebrium (ALT-711), an AGE breaker, combined with nifedipine, a Ca(2+) channel blocker, in a rat model of streptozotocin-induced DH. Compared with monotherapy, combination treatment significantly decreased systolic and diastolic blood pressure values, increased the pulse pressure, and decreased the coefficient of variation of the systolic blood pressure. Plasma biochemistry indicated that the concentrations of prostacyclin and nitric oxide were increased. Gene expression analysis showed significantly decreased prepro-endothelin-1expression in the aorta. These results reveal that alagebrium significantly improves the anti-hypertensive actions of nifedipine in a rat model of DH and suggest its potential use in the successful control of clinical DH.
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Bing
authors: B
authors: Zhang
authors: Chinese PLA General Hospital, Beijing, China.
authors: Kunlun
authors: K
authors: He
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Wei
authors: W
authors: Chen
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Xianfa
authors: X
authors: Cheng
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Hao
authors: H
authors: Cui
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Wu
authors: W
authors: Zhong
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Song
authors: S
authors: Li
authors: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors: Lili
authors: L
authors: Wang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D004359:Drug Therapy, Combination; D019332:Endothelin-1 / Q000097:blood; D011464:Epoprostenol / Q000097:blood; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009543:Nifedipine / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000627:therapeutic use*
chemical_list: D000959:Antihypertensive Agents; D019332:Endothelin-1; D013844:Thiazoles; D009569:Nitric Oxide; D011464:Epoprostenol; C406794:alagebrium; D009543:Nifedipine