ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models

被引:61
作者
Melo, LG
Steinhelper, ME
Pang, SC
Tse, Y
Ackermann, U
机构
[1] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA
[2] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada
[3] Brigham & Womens Hosp, Boston, MA 02115 USA
[4] Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA
[5] Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada
关键词
atrial natriuretic peptide; gene knockout; transgenic; renin-angiotensin system; salt-sensitive hypertension; cardiovascular sympathetic tone;
D O I
10.1152/physiolgenomics.2000.3.1.45
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The recent development of genetic mouse models presenting life-long alterations in expression of the genes for atrial natriuretic peptide (ANP) or its receptors (NPR-A, NPR-C) has uncovered a physiological role of this hormone in chronic blood pressure homeostasis. Transgenic mice overexpressing a transthyretin-ANP fusion gene are hypotensive relative to the nontransgenic littermates, whereas mice harboring functional disruptions of the ANP or NPR-A genes are hypertensive compared with their respective wild-type counterparts. The chronic hypotensive action of ANP is determined by vasodilation of the resistance vasculature, which is probably mediated by attenuation of vascular sympathetic tone at one or several prejunctional sites. Under conditions of normal dietary salt consumption, the hypotensive action of ANP is dissociated from the natriuretic activity of the hormone. However, during elevated dietary salt intake, ANP-mediated antagonism of the renin-angiotensin system is essential for maintenance of blood pressure constancy, inasmuch as the ANP gene "knockout" mice (ANP -/-) develop a salt-sensitive component of hypertension in association with failure to adequately downregulate plasma renin activity. These findings imply that genetic deficiencies in ANP or natriuretic receptor activity may be underlying causative factors in the etiology of salt-sensitive variants of hypertensive disease and other sodium-retaining disorders, such as congestive heart failure and cirrhosis.
引用
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页码:45 / 58
页数:14
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