title: Combination Therapy of Nifedipine and Sulphonylureas Exhibits a Mutual Antagonistic Effect on the Endothelial Cell Dysfunction Induced by Hyperglycemia Linked to Vascular Disease.
abstract: OBJECTIVE
  By inducing severe endothelial impairment, hypertension and diabetes are two leading causes of morbidity and mortality. Hypertensive patients with concomitant diabetes must take both antihypertensive and hypoglycaemic medications, for which there is a lack of experimental and clinical guidelines. This study aimed to examine the interaction between these two types of medication on the endothelial cell function.
  
  
  METHODS
  The effect of antihypertensive (nifedipine and irbesartan) and anti-diabetic (metformin and glibenclamide/glimepiride) drugs on human umbilical vein cells (HUVECs) function was examined using a modified Boyden chamber assay. The intracellular NO and O2- levels of HUVECs were detected through flow cytometry.
  
  
  RESULTS
  Our findings showed that nifedipine/sulphonylurea monotherapy significantly attenuated high glucose-induced (33 mM) HUVECs migration incapacity, while combination therapy of nifedipine and glibenclamide/glimepiride showed no protective effect. Both nifedipine/metformin monotherapy and combined therapy significantly mitigated the migration incapacity induced by high glucose in HUVECs. Combined with either metformin or sulphonylureas, irbesartan therapy was able to attenuate the high glucose-induced migration incapacity of HUVECs. Nifedipine monotherapy decreased the O2- levels and increased the NO levels in in vitro-cultured HUVECs treated with high glucose. However, the combination therapy of nifedipine and glibenclamide increased the O2- levels and decreased the NO levels compared to the nifedipine monotherapeutic group.
  
  
  CONCLUSIONS
  The nifedipine and glibenclamide/glimepiride combination exerted a mutual antagonistic effect on the protection from high glucose-induced impairment in endothelial cells, which might be partially attributed to the increased O2- level and decreased NO level. These results imply that calcium channel blockers + sulphonylurea combination therapy warrants further attention in patients suffering from both hypertension and diabetes.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Yang
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.forename: Chuan
authors.initials: C
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Tao
authors.forename: He-Hui
authors.initials: HH
authors.lastname: Xie
mesh_terms: D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects; D003925:Diabetic Angiopathies / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005947:Glucose / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006943:Hyperglycemia / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000077405:Irbesartan; D008687:Metformin / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D013777:Tetrazoles; D008687:Metformin; D009543:Nifedipine; D005947:Glucose; D000077405:Irbesartan; D010100:Oxygen; D005905:Glyburide