Japanese Pharmacological Society Acta Medica Okayama 1347-8613 130 1 2016 Muscarinic acetylcholine receptor M1 and M3 subtypes mediate acetylcholine-induced endothelium-independent vasodilatation in rat mesenteric arteries 24 32 EN Panot Tangsucharit Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Shingo Takatori Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Yoshito Zamami Department of Pharmaceutical Care and Health Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Mitsuhiro Goda Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Poungrat Pakdeechote Department of Physiology, Faculty of Medicine, Khon Kaen University Hiromu Kawasaki Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Fusako Takayama Department of Clinical Pharmaceutical Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University The present study investigated pharmacological characterizations of muscarinic acetylcholine receptor (AChR) subtypes involving ACh-induced endothelium-independent vasodilatation in rat mesenteric arteries. Changes in perfusion pressure to periarterial nerve stimulation and ACh were measured before and after the perfusion of Krebs solution containing muscarinic receptor antagonists. Distributions of muscarinic AChR subtypes in mesenteric arteries with an intact endothelium were studied using Western blotting. The expression level of M1 and M3 was significantly greater than that of M2. Endothelium removal significantly decreased expression levels of M2 and M3, but not M1. In perfused mesenteric vascular beds with intact endothelium and active tone, exogenous ACh (1, 10, and 100 nmol) produced concentration-dependent and long-lasting vasodilatations. In endothelium-denuded preparations, relaxation to ACh (1 nmol) disappeared, but ACh at 10 and 100 nmol caused long-lasting vasodilatations, which were markedly blocked by the treatment of pirenzepine (M1 antagonist) or 4-DAMP (M1 and M3 antagonist) plus hexamethonium (nicotinic AChR antagonist), but not methoctramine (M2 and M4 antagonist). These results suggest that muscarinic AChR subtypes, mainly M1, distribute throughout the rat mesenteric arteries, and that activation of M1 and/or M3 which may be located on CGRPergic nerves releases CGRP, causing an endothelium-independent vasodilatation. No potential conflict of interest relevant to this article was reported.

日本薬学会 Acta Medica Okayama 00316903 128 3 2008 食後高血糖が血管反応性に及ぼす影響 419 424 EN Yoshito Zamami Shingo Takatori Yukiko Iwatani Kosuke Yamawaki Satoko Miyashita Nana Yabumae Fusako Takayama Mitsunobu Mio Hiromu Kawasaki Recent clinical studies demonstrated that transient postprandial hyperglycemia and hyperinsulinemia may contribute to the development of hypertension. Therefore, we investigated influence of acute hyperglycemia and/or hyperinsulinemia induced by glucose or insulin infusion on neuronal and humoral control of vascular tone in rats. Euglycemic male Wistar rats were pithed under anesthesia and arterial blood pressure was measured. Changes in vascular responses to spinal cord stimulation (SCS) and intravenous bolus injections of noradrenaline, angiotensin II, calcitonin generelated peptide (CGRP), acetylcholine and sodium nitroprusside (SNP) were studied by infusing various concentration of glucose or insulin. Continuous glucose infusion, which increased both blood glucose and serum insulin levels, significantly augmented adrenergic nerve-mediated pressor responses to SCS without affecting injection of pressor responses to noradrenaline or angiotensin II. In pithed rats with artificially increased blood pressure and blockade of autonomic outflow, glucose infusion attenuated CGRPergic nerve-depressor responses to SCS without affecting depressor responses to injection of CGRP, acetylcholine or SNP. In pithed rats treated with octreotide, which increased blood glucose without increasing serum insulin levels, glucose infusion caused only significant augmentation of adrenergic nervemediated pressor responses. Combined infusion of insulin and glucose, which resulted in increased serum insulin levels with euglycemic, significantly augmented adrenergic nerve-mediated pressor responses and attenuated CGRPergic nerve-mediated depressor responses. The present results suggest that acute hyperglycemia and hyperinsulinemia increases adrenergic nerve-mediated vasoconstriction, which is partly associated with the blunted CGRPergic nerve function, and that plasma insulin concentration associated with hyperglycemia may be responsible for alteration of neuronal vascular regulation. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 63 2 2009 Beneficial effects of Vitis coignetiae Pulliat leaves on nonalcoholic steatohepatitis in a rat model 105 111 EN Fusako Takayama Kazuo Nakamoto Hiromu Kawasaki Mitsumasa Mankura Toru Egashira Keiji Ueki Azusa Hasegawa Shigeru Okada Akitane Mori Original Article 10.18926/AMO/31835 <p>Vitis coignetiae Pulliat (Yamabudo) is used as a health juice and wine based on the abundant polyphenols and anthocyanins in its fruit. However, it is not known whether the leaves of this plant confer similar benefits. This study investigated the hepatoprotective effects of aqueous extracts from Vitis coignetiae Pulliat leaves (VCPL) in an animal model of nonalcoholic steatohepatitis (NASH). Rats were fed a choline-deficient high-fat diet for four weeks to generate fatty livers. NASH was induced by oxidative stress loading. Ten weeks later, blood and liver samples were collected from anesthetized animals and assessed biochemically, histologically, and histochemically to determine the extent of oxidative stress injury and the overall effects of VCPL. Six-week VCPL extract supplementation reduced serum levels of liver enzymes, decreased CYP2E1 induction, increased plasma antioxidant activities and delayed the progression of liver fibrosis. The findings suggested that VCPL has strong radical-scavenging activity and may be beneficial in preventing NASH progression.</p> No potential conflict of interest relevant to this article was reported.