Relationship of renin-angiotensin system and ET-1 system activation in long-lasting response to postural changes

Abstract

The present study was performed in seven healthy subjects (aged 22-35 years) to investigate 1) whether plasma and urinary endothelin-1 (ET-1) are involved in the response to postural changes and 2) the relationship between ET-1 formation and the renin-angiotensin system (RAS). Six hours of standing caused a prompt but very short-lasting increase in plasma ET-1 concentration (59% after 5 min, 12% after 1 h) and a notable and sustained enhancement of urinary ET-1 excretion (from 0.59 +/- 0.10 to 1.43 +/- 0.28 pg/min, or 142%; P < 0.001). Plasma renin activity increased by 169% after 1 h of standing. A parallel contraction of urinary volume (-62%), sodium excretion (-55%), and free water reabsorption (-24%) occurred. The return to the supine position after 6 h of orthostasis caused a reduction to baseline values of the ET-1 urinary excretion and urinary volume within 2 h. Inhibition of angiotensin-converting enzyme blunted, but did not eliminate, the orthostasis-induced increase in ET-1 urinary excretion (100%, P < 0.002) and changes in the renal functions. The present results indicate that renal ET-1 is involved in the hemodynamic long-lasting responses to postural changes and that its increase is partially controlled by RAS and suggest that ET-1 might play a role in the regulation of renal function in humans.