Alterations in EDHF-type relaxation and phosphodiesterase activity in mesenteric arteries from diabetic rats

• Published in: American journal of physiology. Heart and circulatory physiology 2003-07, Vol.285 (1), p.H283-H291
• Main Authors: Matsumoto, Takayuki, Kobayashi, Tsuneo, Kamata, Katsuo
• Format: Article
• Language: English
• Subjects: 3',5'-Cyclic-AMP Phosphodiesterases - metabolism; Acetylcholine - pharmacology; Animals; Biological Factors - pharmacology; Blood Glucose - metabolism; Blotting, Western; Body Weight - drug effects; Cyclic AMP - metabolism; Diabetes Mellitus, Experimental - enzymology; Diabetes Mellitus, Experimental - physiopathology; DNA Primers - pharmacology; Endothelium, Vascular - physiology; Isometric Contraction - drug effects; Male; Mesenteric Artery, Superior - drug effects; Mesenteric Artery, Superior - enzymology; Muscle Relaxation - drug effects; Muscle, Smooth, Vascular - drug effects; Precipitin Tests; Rats; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Vasodilator Agents - pharmacology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00954.2002

Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan Submitted 5 November 2002 ; accepted in final form 19 March 2003 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 18 -glycyrrhetinic acid (18 -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. endothelium-derived hyperpolarizing factor; adenosine 3',5'-cyclic monophosphate; streptozotocin Address for reprint requests and other correspondence: K. Kamata, Dept. of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi Univ., Shinagawa-ku, Tokyo 142-8501, Japan (E-mail: kamata{at}hoshi.ac.jp ).