In:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, American Physiological Society, Vol. 280, No. 5 ( 2001-05-01), p. R1322-R1331
Abstract:
Angiotensin (ANG) II effects may be partly mediated by endothelin (ET)-1. This study analyses the hemodynamic, renal, and hormonal responses of acute ET A receptor antagonism (LU-135252) at two ANG II plasma levels in eight conscious dogs. Protocol 1 involved a 60-min baseline, followed by two doses of ANG II for 60 min each (4 and 20 ng · kg −1 · min −1 ), termed ANG II 4 (slightly increased) and ANG II 20 (pathophysiologically increased ANG II plasma concentration). Protocol 2 was the same as protocol 1 but included 15 mg/kg iv LU-135252 after the baseline period. Protocol 3 was a 3-h time control. ANG II without LU-135252 did not increase plasma big ET-1 and ET-1, whereas LU-135252 increased ET-1 transiently after injection. This transient ET-1 increase was not reflected in urinary ET-1 excretion. The ANG II induced decreases in sodium, water, and potassium excretion, glomerular filtration rate, and fractional sodium excretion were not different with and without LU-135252. Mean arterial pressure increased during ANG II and was not lower with LU-135252 (−6 mmHg, not significant). Most importantly, during ANG II 20 LU-135252 prevented the decrease in cardiac output. Simultaneously, systemic vascular resistance increased 40% less, pulmonary vascular resistance was maintained at baseline levels, and central venous and wedge pressure were lower. Because ANG II stimulated endothelin de novo synthesis should just have started after 2 h of ANG II infusion, there must be mechanisms other than blocking the coupling of de novo synthesized endothelins to the ET A receptors to explain the effects of acute ET A receptor inhibition in our setting.
Type of Medium:
Online Resource
ISSN:
0363-6119
,
1522-1490
DOI:
10.1152/ajpregu.2001.280.5.R1322
Language:
English
Publisher:
American Physiological Society
Publication Date:
2001
detail.hit.zdb_id:
1477297-8
SSG:
12
