Losartan normalizes endothelium-derived hyperpolarizing factor-mediated relaxation by activating Ca2+-activated K+ channels in mesenteric artery from type 2 diabetic GK rat. 2010

Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.

Ca(2+)-activated K(+) (K(Ca)) channels are important for endothelium-derived hyperpolarizing factor (EDHF) signaling. Since treatment with angiotensin II receptor blockers (ARBs) improves vasculopathies in type 2 diabetic patients, we asked whether the EDHF-type relaxation and its associated K(Ca) channels [small (SK(Ca))-, intermediate (IK(Ca))-, and large (BK(Ca))-conductance channels] are abnormal in mesenteric arteries isolated from Goto-Kakizaki (GK) rats at the chronic stage of type 2 diabetes (34 - 38 weeks) and whether an ARBs (losartan, 25 mg . kg(-1) . day(-1) for 2 weeks) might correct these abnormalities. Although the acetylcholine chloride-induced EDHF-type relaxation in mesenteric arteries from GK rats was reduced versus the Wistar controls, it was significantly restored by losartan treatment. The SK(Ca)-blocker apamin or the IK(Ca)-blocker 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) inhibited such relaxations in the losartan-treated or -untreated Wistar groups and in the losartan-treated GK group, but not in the losartan-untreated GK group. The BK(Ca)-blocker iberiotoxin had a significant inhibitory effect in only one of these groups, the losartan-treated GK. The relaxations induced by the SK(Ca)/IK(Ca) activator NS309 and the BK(Ca) activator NS1619, which were impaired in GK rats, were normalized by losartan treatment. We conclude that losartan improves EDHF-type relaxation in GK rats at least partly by normalizing SK(Ca)/IK(Ca) activities and increasing BK(Ca) activity.

UI MeSH Term Description Entries
D008297 Male Males
D008638 Mesenteric Arteries Arteries which arise from the abdominal aorta and distribute to most of the intestines. Arteries, Mesenteric,Artery, Mesenteric,Mesenteric Artery
D003924 Diabetes Mellitus, Type 2 A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY. Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,MODY,Maturity-Onset Diabetes Mellitus,NIDDM,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Noninsulin Dependent,Diabetes Mellitus, Noninsulin-Dependent,Diabetes Mellitus, Type II,Maturity-Onset Diabetes,Noninsulin-Dependent Diabetes Mellitus,Type 2 Diabetes,Type 2 Diabetes Mellitus,Adult-Onset Diabetes Mellitus,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Slow Onset,Diabetes, Maturity-Onset,Diabetes, Type 2,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes,Maturity Onset Diabetes Mellitus,Non-Insulin-Dependent Diabetes Mellitus,Noninsulin Dependent Diabetes Mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004730 Endothelium, Vascular Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components. Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001685 Biological Factors Endogenously synthesized compounds that influence biological processes not otherwise classified under ENZYMES; HORMONES or HORMONE ANTAGONISTS. Biologic Factors,Biological Factor,Factor, Biologic,Factor, Biological,Factors, Biological,Biologic Factor,Factors, Biologic
D014664 Vasodilation The physiological widening of BLOOD VESSELS by relaxing the underlying VASCULAR SMOOTH MUSCLE. Vasodilatation,Vasorelaxation,Vascular Endothelium-Dependent Relaxation,Endothelium-Dependent Relaxation, Vascular,Relaxation, Vascular Endothelium-Dependent,Vascular Endothelium Dependent Relaxation
D017208 Rats, Wistar A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain. Wistar Rat,Rat, Wistar,Wistar Rats
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

Related Publications

Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
November 2005, American journal of physiology. Heart and circulatory physiology,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
October 1998, Journal of cardiovascular pharmacology,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
June 2015, Biology of reproduction,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
June 2017, Biology of reproduction,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
October 2013, The Journal of physiology,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
January 2001, European journal of pharmacology,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
June 2006, Vascular pharmacology,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
September 2007, The Tohoku journal of experimental medicine,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
January 2020, Biological & pharmaceutical bulletin,
Takayuki Matsumoto, and Keiko Ishida, and Kumiko Taguchi, and Tsuneo Kobayashi, and Katsuo Kamata
December 2002, Journal of cardiovascular pharmacology,
Copied contents to your clipboard!