Inhibition of Ras-GTPase improves diabetes-induced abnormal vascular reactivity in the rat perfused mesenteric vascular bed

被引:6
|
作者
Yousif, MHM
Benter, IF
Abraham, S
Akhtar, S
机构
[1] Kuwait Univ, Fac Med, Dept Pharmacol & Toxicol, Safat 13110, Kuwait
[2] Cardiff Univ, Welsh Sch Pharm, Ctr Genome Based Therapeut, Cardiff, S Glam, Wales
关键词
diabetes; Ras-GTPase; norepinephrine; endothelin-1; angiotensin II; carbachol; histamine; mesenteric bed;
D O I
10.1159/000075629
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: The signalling mechanisms involved in regulating altered vascular reactivity in diabetes are not fully understood. The aim of this study was to investigate the role of Ras-GTPase in the development of abnormal vascular reactivity in diabetes. Materials and Methods: We investigated the ability of chronic administration of FPTIII (1.5 mg/kg), an inhibitor of Ras-GTPase, to modulate the altered vasoreactivity of the rat perfused mesenteric bed to common vasoconstrictors and vasodilators in streptozotocin (STZ)-induced diabetes. Results: The vasoconstrictor responses induced by norepinephrine (NE) and endothelin-1 (ET-1) were significantly increased whereas vasodilator responses to carbachol, histamine and isoprenaline were significantly reduced in the perfused mesenteric bed of the STZ-diabetic rats. Inhibition of Ras-GTPase by chronic administration of FPTIII produced a significant normalization of the altered agonist-induced vasoconstrictor and vasodilator responses without affecting blood glucose levels. Inhibition of Ras-GTPase did not affect the agonist-induced vasoconstrictor and vasodilator responses in the control animals. Conclusion: These data suggest that signal transduction pathways activated by Ras-GTPase are involved in the development of diabetic vascular dysfunction. Potential strategies aimed at modifying actions of signal transduction pathways involving Ras-GTPase may therefore prove to be beneficial in treatment of vascular complications in diabetes. Copyright (C) 2004 S. Karger AG, Basel.
引用
收藏
页码:57 / 62
页数:6
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