Nephrogenic diabetes insipidus in mice lacking all nitric oxide synthase isoforms

Tsuyoshi Monshita, Masato Tsutsui, Hiroaki Shimokawa, Ken Sabanai, Hiromi Tasaki, Osamu Suda, Sei Nakata, Akihide Tanimoto, Ke Yong Wang, Yoichi Ueta, Yasuyuki Sasaguri, Yasuhide Nakashima, Nobuyuki Yanagihara

研究成果: Article査読

114 被引用数 (Scopus)

抄録

Nitric oxide (NO) is produced in almost all tissues and organs, exerting a variety of biological actions under physiological and pathological conditions. NO is synthesized by three different isoforms of NO synthase (NOS), including neuronal, inducible, and endothelial NOSs. Because there are substantial compensatory interactions among the NOS isoforms, the ultimate roles of endogenous NO in our body still remain to be fully elucidated. Here, we have successfully developed mice in which all three NOS genes are completely deleted by crossbreeding singly NOS-/- mice. NOS expression and activities were totally absent in the triply NOS-/- mice before and after treatment with lipopolysaccharide. Although the triply NOS-/- mice were viable and appeared normal, their survival and fertility rates were markedly reduced as compared with the wild-type mice. Furthermore, these mice exhibited marked hypotonic polyuria, polydipsia, and renal unresponsiveness to an antidiuretic hormone, vasopressin, all of which are characteristics consistent with nephrogenic diabetes insipidus. In the kidney of the triply NOS-/- mice, vasopressin-induced cAMP production and membranous aquaporin-2 water channel expression were reduced associated with tubuloglomerular lesion formation. These results provide evidence that the NOS system plays a critical role in maintaining homeostasis, especially in the kidney.

本文言語English
ページ(範囲)10616-10621
ページ数6
ジャーナルProceedings of the National Academy of Sciences of the United States of America
102
30
DOI
出版ステータスPublished - 2005 7 26
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