Relationship between PDK1 and contraction in carotid arteries in Goto-Kakizaki rat, a spontaneous type 2 diabetic animal model

• Published in: Canadian journal of physiology and pharmacology 2017-04, Vol.95 (4), p.459-462
• Main Authors: Watanabe, Shun, Matsumoto, Takayuki, Taguchi, Kumiko, Kobayashi, Tsuneo
• Format: Article
• Language: English
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; 3-Phosphoinositide-Dependent Protein Kinases - antagonists & inhibitors; 3-Phosphoinositide-Dependent Protein Kinases - metabolism; Animals; artère carotide; Carotid arteries; Carotid Arteries - drug effects; Carotid Arteries - physiology; carotid artery; Chronic Disease; contraction; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetic Angiopathies - drug therapy; Diabetic Angiopathies - etiology; Diabetic Angiopathies - metabolism; diabète de type 2; Disease Models, Animal; GK rat; Health aspects; Indazoles - pharmacology; Kinases; Male; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; PDK1; Phenylephrine - pharmacology; Protein kinases; Pyrimidines - pharmacology; rat GK; Rats; Rats, Wistar; Rodents; Serotonin; Serotonin - pharmacology; Signal Transduction; Thromboxane A2 - analogs & derivatives; Type 2 diabetes; Vasoconstriction - drug effects; Vasoconstrictor Agents - pharmacology
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/cjpp-2016-0372

We studied the relationship between 3-phosphoinositide-dependent protein kinase 1 (PDK1) and contractions induced by serotonin, phenylephrine, and thromboxane A 2 mimetic (U46619) in the presence of nitric oxide synthase inhibitor in the carotid arteries of Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic model, in the chronic stage of disease. Serotonin-induced contraction was greater in the GK rats than in the control Wistar rats. A specific PDK1 inhibitor (GSK2334470) decreased the serotonin-induced contraction in the GK rats but not in the Wistar rats, and the difference in such contraction was abolished with this treatment. In GK rats, phenylephrine-induced contraction exhibited a leftward shift and U46619-induced contraction was greater still. Phenylephrine- and U46619-induced contractions were reduced by GSK2334470 in both groups. These results suggest, for the first time, that the contribution of PDK1 is different among 3 vasoconstrictors and that PDK1 contributed to increased serotonin-induced contraction in the carotid arteries of GK rats.