Vascular effect of insulin as a vasoactive peptide and its resistance

Research Project

Project/Area Number	11672261
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	応用薬理学・医療系薬学
Research Institution	OKAYAMA UNIVERSITY
Principal Investigator	KAWASAKI Hiromu Okayama University, Graduate School of Natural Science and Technology, Professor, 大学院・自然科学研究科, 教授 (60125151)
Co-Investigator(Kenkyū-buntansha)	KUROSAKI Yuji Okayama University, Graduate School of Natural Science and Technology, Associate Professor, 大学院・自然科学研究科, 助教授 (90161786)
Project Period (FY)	1999 – 2000
Project Status	Completed (Fiscal Year 2000)
Budget Amount *help	¥3,600,000 (Direct Cost: ¥3,600,000) Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywords	INSULIN / VASCULAR RESPONSIVENESS / PERIARTERIAL NERVE FUNCTION / INSULIN-RESISTANT RAT / CALCITONIN GENE-RELATED PEPTIDE-CONTAINING NERVE / MESENTERIC RESISTANCE ARTERY / ADRENERGIC NERVE / 含硫アミノ酸タウリン / 血管内皮機能 / 交感神経 / 血管拡張性神経
Research Abstract	Vascular responsiveness and effect of long-term treatment (4 weeks) with troglitazone, taurine, L-compound (novel angiotensin II antagonist) or combined treatment of both drugs on vascular responsiveness were studied in the mesenteric artery of fructose-fed insulinresistant rats. Male SD rats (6-week-old) were divided into six groups : control group ; high-fructose (60%) chow-fed group (FFR), 0.2% troglitazone-treated FFR, taurine (3%) in drinking water-treated FFR, 0.002% L-compound-treated FFR or 0.2% troglitazone plus 3% taurine-treated FFR.After the 10-hr fast, blood samples were obtained, and mean blood pressure (MBP) were measured. There was no significant difference in blood glucose and MBP among each groups, whereas serum immunoreactiveinsulin and triglyceride value were higher in FFR than in normal rat. Taurine, troglitazone, L-compound or troglitazone+taurine treatment decreased serum levels of insulin and triglyceride in FFR.In perfused mesenteric vascular beds, periarterial nerve stimulation (PNS)-induced vasoconstriction was greater in FFR than in control. Treatment with troglitazone but not taurine reduced PNS-induced vasoconstriction. In preparation with active tone by methoxamine in the presence of guanethidine, calcitonin gene-related peptide (CGRP)-and sodium nitroprusside-induced vasodilation were no change among each groups. PNS-, acetylcholine-, and insulin-induced vasodilation were smaller in FFR than in normal rat. Taurine, troglitazone, L-compound or troglitazone +taurinetreatment augmented these responses. These results suggest that, in mesenteric artery of FFR, taurine as well as troglitazone restores decreased CGRP-nerved function, endothelial function and insulin-induced vasodilation.