Impairment of α1‐adrenoceptor‐mediated contractile activity in caudal arterial smooth muscle from Type 2 diabetic Goto‐Kakizaki rats

1. In the present study, we compared the responsiveness of de‐endothelialized caudal artery smooth muscle strips, isolated from Type 2 diabetic Goto‐Kakizaki (GK) and normal Wistar rats, to α₁‐adrenoceptor stimulation (cirazoline) and membrane depolarization (K⁺). 2. The contractile and myosin 20 kDa light chain (LC₂₀) phosphorylation responses to 0.3 μmol/L cirazoline of caudal artery strips isolated from 12‐week‐old GK rats were significantly reduced compared with those of age‐matched Wistar rats, whereas the contractile and LC₂₀ phosphorylation responses to 60 mmol/L K⁺ were unaltered. 3. Stimulation of fura 2‐AM‐loaded strips from GK rats with 0.3 μmol/L cirazoline induced a significantly smaller rise in [Ca²⁺]_i (by ～20%) compared with that in strips from Wistar rats, whereas comparable Ca²⁺ transients were evoked by K⁺ in both. 4. Using quantitative polymerase chain reaction, no significant differences were detected in the mRNA expression of α_1A‐, α_1B‐ and α_1D‐adrenoceptor subtypes between GK and Wistar rats. 5. Cirazoline (1 μmol/L)‐ and caffeine (20 mmol/L)‐induced contractions in the absence of extracellular Ca²⁺ were unaltered in GK rats, suggesting that the release of Ca²⁺ from the sarcoplasmic reticulum in response to cirazoline does not differ between GK and Wistar rats. 6. The results of the present study suggest that Ca²⁺ entry from the extracellular space via α₁‐adrenoceptor‐activated, Ca²⁺‐permeable channels, but not via membrane depolarization and voltage‐gated L‐type Ca²⁺ channels, is impaired in caudal artery smooth muscle of GK rats.