Effects of chronic administration of the novel endothelin antagonist J-104132 on endothelial dysfunction in streptozotocin-induced diabetic rat.

ABSTRACT: 1. The biosynthesis of endothelin-1 is increased in the diabetic state. So this peptide may cause diabetic vascular complications. We tested this possibility by chronically administering J-104132, a potent orally active mixed antagonist of endothelin A and B (ET(A)/ET(B)) receptors to streptozotocin (STZ)-induced diabetic rats and focusing on changes in endothelial function. 2. The acetylcholine (ACh)-induced endothelium-dependent relaxation was impaired in diabetic rats and this impairment was significantly attenuated following chronic administration of J-104132 (10 mg kg(-1), p.o., daily for 4 weeks). 3. In an in vitro experiment using aortae from diabetic rats, the ACh-induced relaxation was not changed by the presence of J-104132 (3 x 10(-9) M). 4. The expression levels of the mRNA for

SUBMITTER: Kanie N 

PROVIDER: S-EPMC1573322 | biostudies-literature | 2002 Apr

REPOSITORIES: biostudies-literature