Impaired myogenic tone in isolated cerebral and coronary resistance arteries from the goto-kakizaki rat model of type 2 diabetes

Abstract

Aim: 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 [Ca 2+] 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 [Ca 2+] 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. Conclusion: 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. © 2012 S. Karger AG, Basel.