[Effect of ET-1 antisense oligodeoxynucleotide on the hemodynamics of normal and experimental hypertensive rats].
It was previously found that a phosphorothioated antisense oligodeoxynucleotide (ETASODN) significantly inhibits production of endothelin-1 (ET-1). The purpose of the present study was to determine whether intracerebroventricular injection of ETASODN targeted to prepro-ET-1 is capable of exerting the same preventing effect on the aorta narrowing of experimentally modeled hypertensive rats. Radioimmunoassay showed that ET-1 level in the brain stem of hypertensive rats was significantly elevated. In addition to down-regulating the ET-1 level, astisense could also reduce mean arterial pressure (MAP), heart rate and LVSP in model rats. The antisense also down-regulated the ET-1 level in hypothalamus and brain stem, reducing MAP in normal control rats. After treatment with the antisense, the value of delta MAP was markedly lowered in experimental hypertensive rats as compared to the control ones. Thus it appears that (1) ET-1 might play an important role in central cardiovascular regulation in rats and (2) antisense ETASODN might be used in treatment of hypertension via inhibiting ET-1 production.
Du
Y P
YP
Department of Pathophysiology, Tongji Medical University, Wuhan 430030.
Hu
Q H
QH
Wang
J Z
JZ
Wang
D X
DX
D000818:Animals; D001921:Brain / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D019332:Endothelin-1; D020319:Oligodeoxyribonucleotides, Antisense