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 alpha(1)-adrenoceptor stimulation (cirazoline) and membrane depolarization (K(+)). 2. The contractile and myosin 20 kDa light chain (LC(20)) phosphorylation responses to 0.3 micromol/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 LC(20) phosphorylation responses to 60 mmol/L K(+) were unaltered. 3. Stimulation of fura 2-AM-loaded strips from GK rats with 0.3 micromol/L cirazoline induced a significantly smaller rise in [Ca(2+)](i) (by approximately 20%) compared with that in strips from Wistar rats, whereas comparable Ca(2+) 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 micromol/L)- and caffeine (20 mmol/L)-induced contractions in the absence of extracellular Ca(2+) were unaltered in GK rats, suggesting that the release of Ca(2+) 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 Ca(2+) entry from the extracellular space via alpha(1)-adrenoceptor-activated, Ca(2+)-permeable channels, but not via membrane depolarization and voltage-gated L-type Ca(2+) channels, is impaired in caudal artery smooth muscle of GK rats.
Department of Pharmacodynamics, Meiji Pharmaceutical University, Tokyo, Japan. mitsuom@my-pharm.ac.jp
Mitsuo
M
Mita
Takuto
T
Kuramoto
Kazushi
K
Ito
Natsuko
N
Toguchi-Senrui
Shigeru
S
Hishinuma
Michael P
MP
Walsh
Masaru
M
Shoji
D058646:Adrenergic alpha-1 Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D058646:Adrenergic alpha-1 Receptor Agonists; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; C014282:cirazoline