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

P>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 alpha(1)-adrenoceptor stimulation (cirazoline) and membrane depolarization (K+). 2. The contractile and myosin 20 kDa light chain (LC20) phosphorylation responses to 0.3 mu mol/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 mu mol/L cirazoline induced a significantly smaller rise in [Ca2+](i) (by similar to 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 alpha(1A)-, alpha(1B)- and alpha(1D)-adrenoceptor subtypes between GK and Wistar rats. 5. Cirazoline (1 mu mol/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 alpha(1)-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.