ANP in regulation of arterial pressure and fluid-electrolyte balance: lessons from genetic mouse models.
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.
Melo
L G
LG
Department of Physiology, University of Toronto, Toronto, Ontario, Canada M5S 1A8. lmelo@rics.bwh.harvard.edu
Steinhelper
M E
ME
Pang
S C
SC
Tse
Y
Y
Ackermann
U
U
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics; D004195:Disease Models, Animal; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism; D007022:Hypotension / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D012084:Renin-Angiotensin System / Q000235:genetics; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology; D014664:Vasodilation / Q000235:genetics; D014882:Water-Electrolyte Balance / Q000235:genetics*
D012965:Sodium Chloride; D009320:Atrial Natriuretic Factor