期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:1978
卷号:75
期号:2
页码:975-979
DOI:10.1073/pnas.75.2.975
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:The mechanism of increased adrenal sensitivity to angiotensin II during the aldosterone response to sodium restriction was investigated in the rat. Sodium restriction for 36 hr markedly increased the aldosterone-stimulating effect of low-dose (1 ng/min) infusion of angiotensin II and caused enhanced binding of 125I-labeled angiotensin II to the zona glomerulosa in vivo. Conversely, in vivo binding of 125I-labeled angiotensin II was significantly decreased after 36 hr of high-sodium intake. In isolated glomerulosa cells, the increased binding of angiotensin II after sodium restriction was shown to result from a significant increase in receptor affinity (+80%) and a smaller increase in receptor concentration (+25%). The corresponding aldosterone responses in dispersed cells showed an increase in sensitivity to angiotensin II, commensurate with the increased receptor affinity. More prolonged sodium restriction (4 days) caused a further increase in angiotensin receptor concentration (+70%) and maximal aldosterone response (+50%), whereas the binding affinity of adrenal receptors and the sensitivity of the in vitro aldosterone response had returned to normal. During sodium loading for 36 hr and 4 days, the converse effects on adrenal angiotensin II receptors and aldosterone production were observed. Also, in contrast to the consistent increase in angiotensin II receptors in the adrenal glands of sodium-restricted animals, the angiotensin II binding capacity of uterine smooth muscle was decreased by 40% after 7 days of sodium restriction. The rapid regulation of receptor affinity and concentration during changes in sodium intake provides a basis for the dynamic modulation of aldosterone responses by dietary sodium content. During sodium restriction, the sequential changes in receptor affinity and concentration account for the enhanced binding and steroidogenic actions of angiotensin II in vivo and in vitro. These receptor changes, and the converse effects of sodium loading, serve as a local regulatory mechanism in the physiological control of adrenal sensitivity and aldosterone secretion. The opposite finding in smooth muscle--that sodium restriction decreases the concentration of angiotensin II receptors--is consistent with the divergent effects of changing sodium balance upon vascular and adrenal responses to angiotensin II.
关键词:angiotensin II receptors ; zona glomerulosa ; sodium balance ; steroidogenesis ; smooth muscle