Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats.
In isolated superior mesenteric artery rings from age-matched control rats and streptozotocin (STZ)-induced diabetic rats, we investigated the role of cAMP in endothelium-derived hyperpolarizing factor (EDHF)-type relaxation. The ACh-induced EDHF-type relaxation was significantly weaker in STZ-induced diabetic rats than in control rats, and in both groups of rats it was attenuated by 18alpha-glycyrrhetinic acid (18alpha-GA), an inhibitor of gap junctions, and enhanced by IBMX, a cAMP-phosphodiesterase (PDE) inhibitor. These enhanced EDHF-type responses were very similar in magnitude between diabetic and age-matched control rats. The EDHF-type relaxation was enhanced by cilostamide, a PDE3-selective inhibitor, but not by Ro 20-1724, a PDE4-selective inhibitor. The expression levels of the mRNAs and proteins for two cAMP PDEs (PDE3A, PDE3B) were significantly increased in STZ-induced diabetic rats, but those for PDE4D were not. We conclude that the impairment of EDHF-type relaxations in STZ-induced diabetic rats may be attributed to a reduction in the action of cAMP via increased PDE activity.
Matsumoto
Takayuki
T
Deparment of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Kobayashi
Tsuneo
T
Kamata
Katsuo
K
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000201:enzymology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011233:Precipitin Tests; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D001786:Blood Glucose; D017931:DNA Primers; D012333:RNA, Messenger; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000109:Acetylcholine