title: A comparison of the hypotensive and hypoglycaemic actions of an angiotensin converting enzyme inhibitor, an AT1a antagonist and troglitazone.
abstract: OBJECTIVE
  To define the relationship between changes in insulin sensitivity and attenuation of hypertension.
  
  
  METHODS
  We investigated whether troglitazone (CS-045, an insulin sensitizer) has an antihypertensive effect in fructose (FRU)-fed Wistar rats with insulin resistance and simultaneously compared its hypotensive efficacy with those of alacepril (ALA, an angiotensin converting enzyme inhibitor) and TCV-116 (an AT1a receptor antagonist). Male rats aged 8 weeks were divided into five groups: controls fed normal chow, a FRU group fed FRU-rich (55%) chow, a FRU plus ALA group fed 30 mg/kg ALA per day, a FRU plus TCV-116 group fed 1 mg/kg TCV-116 per day and a FRU plus CS-045 group fed 70 mg/kg CS-045 per day). After 8 weeks, the body weight and systolic blood pressure were recorded and glucose tolerance was determined by glucose loading (2 g/kg, intraperitoneally) and a steady-state plasma glucose (SSPG) method. The plasma membrane glucose transporter 4 content in gastrocneumius muscle was determined by Western blot analysis.
  
  
  RESULTS
  FRU increased blood pressure from 125 mmHg in controls to 141 mmHg (P < 0.01). ALA and TCV-116 administration decreased blood pressure to 111 and 107 mmHg, respectively (P < 0.01). CS-045 administration lowered blood pressure significantly to 121 mmHg. Area under the curve levels for plasma insulin during glucose loading increased from 1.7 in controls to 3.6 ng/ml x h in FRU-fed rats, but were lowered by the three drugs. SSPG levels increased from 12.5 in controls to 18.3 mmol/l in FRU-fed rats (P < 0.01), but were decreased by ALA and TCV-116 administration (P < 0.01). CS-045 administration also lowered SSPG levels to 15.3 mmol/l (P < 0.05). FRU-feeding induced a 1.24-fold increase in plasma membrane glucose transporter 4, which was not affected by ALA and TCV-116 administration, but was augmented 1.82-fold by CS-045 administration. Furthermore, the increased triglyceride level after FRU was diminished both by ALA and by CS-045 administration.
  
  
  CONCLUSIONS
  These results suggest that, in the insulin-resistant state, troglitazone, an angiotensin converting enzyme inhibitor and an AT1a receptor antagonist show comparable hypotensive and hypoglycaemic effects.
authors.affiliation: Fourth Department of Medicine, Saitama Medical School, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Noguchi
authors.forename: T
authors.initials: T
authors.lastname: Izumida
authors.forename: J
authors.initials: J
authors.lastname: Tatebe
authors.forename: S
authors.initials: S
authors.lastname: Katayama
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000031:analogs & derivatives* / Q000494:pharmacology; D002839:Chromans / Q000494:pharmacology*; D004032:Diet; D005632:Fructose / Q000008:administration & dosage; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles; D013844:Thiazoles / Q000494:pharmacology*; D045162:Thiazolidinediones; D000077288:Troglitazone
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D009004:Monosaccharide Transport Proteins; D013777:Tetrazoles; D013844:Thiazoles; D045162:Thiazolidinediones; D005632:Fructose; D002216:Captopril; D000077288:Troglitazone; C077793:candesartan cilexetil; C046835:alacepril