当前位置： SCI文献检索 > KIDNEY INTERNATIONAL期刊下所有文献 > AT1a receptor knockout in mice impairs urine concentration by reducing basal vasopressin levels and its receptor signaling proteins in the inner medulla.

AT1a receptor knockout in mice impairs urine concentration by reducing basal vasopressin levels and its receptor signaling proteins in the inner medulla.

Abstract：

:Angiotensin II plays an important role in the regulation of blood pressure, body salt and fluid balance, and urine concentration. Mice with deletion of the AT(1a) receptor develop polyuria and urine concentration defects. We studied the mechanisms of these urine concentration defects by treating wild-type and AT(1a)-knockout mice with arginine vasopressin (AVP) for 2 weeks, controlling their water intake, or giving them an osmotic diuretic (sucrose) in order to determine whether central or nephrogenic mechanisms were involved. Under basal conditions, AT(1a)-knockout mice were hypotensive, had lower plasma AVP, and excreted more urine with a markedly reduced osmolality compared with wild-type mice. However, basal glomerular filtration rates were similar in both strains of mice. We isolated total lysate and membrane proteins from the inner medulla of wild-type and mutant mouse kidneys, and found that the amounts of aquaporin 2 (AQP2), adenylyl cyclases III and V/VI, and phosphorylated MAP kinases ERK 1/2 proteins were all reduced in the inner medulla of the knockout mice. Infusion of AVP raised plasma levels and blood pressure proportionally in both strains, but polyuria persisted and urine osmolality remained significantly lower in the knockout mice. Although AVP increased urine osmolality slightly in water-deprived knockout mice, this was well below the basal osmolality of wild-type mice. The diuretic response to the hyperosmotic sucrose was also impaired in the knockout mice. Neither AVP nor water rationing restored the levels of the inner medullary signaling proteins and membrane AQP2 proteins in the knockout mice. We suggest that AT(1a) receptor deletion causes polyuria and urine concentration defects by decreasing basal AVP release and impairing AVP-induced receptor signaling in the inner medulla.

journal_name

Kidney Int

journal_title

Kidney international

authors

Li XC,Shao Y,Zhuo JL

doi

10.1038/ki.2009.134

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

169-77

issue

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)53938-0

journal_volume

pub_type

杂志文章

在线工具

AT1a receptor knockout in mice impairs urine concentration by reducing basal vasopressin levels and its receptor signaling proteins in the inner medulla.