title: Effects of a PPAR-gamma receptor agonist and an angiotensin receptor antagonist on aortic contractile responses to alpha receptor agonists in diabetic and/or hypertensive rats.
abstract: OBJECTIVE
  The aim of this study was to investigate the effects of pioglitazone and losartan pre-treatment on the aortic contractile response to the alpha-1 agonist, phenylephrine, and the alpha-2 agonist, clonidine, in L-NAME-induced hypertensive, STZ-induced diabetic, and hypertensive diabetic rats.
  
  
  METHODS
  Male Wistar rats were randomly allocated to four groups: control, diabetic (DM), hypertensive (HT) and hypertensive diabetic (HT + DM) groups. Three weeks after drug application, in vitro dose-response curves to phenylephrine (Phe) (10-9-10-5M) and clonidine (Clo) (10-9-10-5M) were recorded in aortic rings in the absence (control) and presence of pioglitazone (10 µM) and/or losartan (10 µM).
  
  
  RESULTS
  Pioglitazone and losartan caused a shift to the right in contractile response to phenylephrine in all groups. The sensitivity of the aortic rings to phenylephrine was decreased in the presence of pioglitazone and/or losartan in all groups. The contractile response of clonidine decreased in the presence of pioglitazone and/or losartan in the control, HT and DM groups.
  
  
  CONCLUSIONS
  The sensitivity of aortic rings to alpha-1 and alpha-2 adrenoceptors was decreased in the presence of pioglitazone and/or losartan in diabetic and hypertensive rats. Concomitant use of PPAR-gamma agonists, thiazolidinediones, and angiotensin receptor blockers may be effective treatment for diabetes and hypertension.
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey. Email: ibrahimtugrul@yahoo.com.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Tugrul
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
authors.forename: Turhan
authors.initials: T
authors.lastname: Dost
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
authors.forename: Omer
authors.initials: O
authors.lastname: Demir
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
authors.forename: Filiz
authors.initials: F
authors.lastname: Gokalp
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Oz
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
authors.forename: Necip
authors.initials: N
authors.lastname: Girit
authors.affiliation: Department of Medical Pharmacology, Faculty of Medicine, Adnan Menderes University, Aydin, Turkey.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Birincioglu
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003000:Clonidine / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced; D003925:Diabetic Angiopathies / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology*; D000077205:Pioglitazone; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000316:Adrenergic alpha-Agonists; D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D044140:Receptor, Angiotensin, Type 1; D045162:Thiazolidinediones; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019808:Losartan; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone