title: Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes.
abstract: OBJECTIVE
  Type 2 diabetes is associated with stroke and cardiac dysfunction. We therefore investigated isolated middle cerebral arteries and coronary septal arteries from the diabetic Goto-Kakizaki (GK) rat model of nonobese type 2 diabetes.
  
  
  METHODS
  Myogenic tone and agonist-induced responses were investigated under isobaric conditions with simultaneous recording of [Ca2+]i. Rho-kinase and NO pathways were investigated using specific pharmacological tools.
  
  
  RESULTS
  Arteries from GK rats developed less tone at pressures from 20 to 100 mm Hg than arteries from control Wistar (CW) rats while [Ca2+]i was similar. Blocking the Rho-kinase pathway decreased the pressure-induced development of tone and after blockade no difference in myogenic tone between arteries from GK and CW rats was seen. Cerebral arteries had similar tone to a maximal concentration of U46619 (GK: 35.5±2% vs. CW: 31.6±5%), while coronary arteries from GK rats developed less tone than arteries from CW rats (12±3 vs. 26.1±3%). Endothelium-dependent vasodilation to A23187 (cerebral) and to acetylcholine (coronary) was not different between arteries from GK and CW rats.
  
  
  CONCLUSIONS
  Our data suggest that in resistance arteries from the brain and the heart of GK rats the myogenic tone is decreased due to impaired calcium sensitivity likely due to a defective Rho-kinase pathway.
authors.affiliation: NeuroSearch A/S, Ballerup, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Kold-Petersen
authors.forename: E
authors.initials: E
authors.lastname: Brøndum
authors.forename: H
authors.initials: H
authors.lastname: Nilsson
authors.forename: A
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: C
authors.initials: C
authors.lastname: Aalkjaer
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D002118:Calcium / Q000378:metabolism; D003331:Coronary Vessels / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology / Q000503:physiopathology*; D009569:Nitric Oxide / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D000577:Amides; D001786:Blood Glucose; D011725:Pyridines; C108830:Y 27632; D009569:Nitric Oxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D054460:rho-Associated Kinases; D011493:Protein Kinase C; D002118:Calcium