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

• Published in: Clinical and experimental pharmacology & physiology 2010-03, Vol.37 (3), p.350-357
• Main Authors: Mita, Mitsuo, Kuramoto, Takuto, Ito, Kazushi, Toguchi-Senrui, Natsuko, Hishinuma, Shigeru, Walsh, Michael P, Shoji, Masaru
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Agonists - pharmacology; Animals; Arteries - drug effects; Arteries - physiopathology; Ca2+ mobilization; diabetes; Diabetes Mellitus, Type 2 - physiopathology; Goto-Kakizaki rats; Imidazoles - pharmacology; In Vitro Techniques; Male; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiopathology; Rats; Rats, Wistar; Receptors, Adrenergic, alpha-1 - physiology; vascular smooth muscle; Vasoconstriction - drug effects; Vasoconstriction - physiology; α1-adrenoceptors
• ISSN: 0305-1870; 1440-1681
• DOI: 10.1111/j.1440-1681.2009.05308.x

Summary 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 α1A‐, α1B‐ and α1D‐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.