A comparison of spasmogenic and relaxant responses in aortae from C57/BL/KsJ diabetic mice with those from their non-diabetic litter mates.
We have investigated the responsiveness of thoracic aorta from the C57/BL/KsJ-db/db mouse (a model of type II diabetes) using a small-vessel myograph. The maximum tension developed in response to phenylephrine was greater in diabetic mice compared with non-diabetic (+/?) mice (2.7 +/- 0.1 and 1.8 +/- 0.1 mN/mm, respectively). Responses to phenylephrine were enhanced in tissues from both phenotypes when preincubated with L-NAME (100 mumol/l) and after the addition of oxyhaemoglobin (3 mumol/l), suggesting that endogenous NO release occurs in both. The maximum relaxation to carbachol was less in db/db mice (32 +/- 4%) than in +/? mice (49 +/- 5%) whilst that to sodium nitroprusside was similar (> 90%). However, the concentration-effect curve to both vasorelaxants in db/db mice lay to the right of that in the +/? mice. These results suggest that the responsiveness of the vasculature is altered in the db/db mouse. Since this mouse is a model of type II diabetes this may be a consequence of hyperglycaemia and/or insulin resistance.
Piercy
V
V
SmithKline Beecham Pharmaceuticals, Harlow, UK. Val-Piercy-l@sbphrd.com
Taylor
S G
SG
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000502:physiology; D003920:Diabetes Mellitus / Q000235:genetics / Q000503:physiopathology*; D004032:Diet; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D009213:Myography; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D018721:Muscarinic Agonists; D014662:Vasoconstrictor Agents; D019001:Nitric Oxide Synthase