Hypotension and bradycardia during caloric restriction in mice are independent of salt balance and do not require ANP receptor.
We hypothesized that caloric restriction (CR)-induced hypotension would correlate with increased sodium excretion through an atrial natriuretic peptide (ANP)-dependent mechanism. To test this hypothesis, the cardiovascular parameters of c57/Bl mice were measured with radiotelemetry while urine was collected. The 23-h mean blood pressure (BP) dropped from 108.6 +/- 1.8 to 92.7 +/- 2.4 mmHg, and 23-h heart rate dropped from 624 +/- 5 to 426 +/- 13 beats/min over 7 days of CR at 29 degrees C. Contrary to our hypothesis, urine sodium excretion decreased by 55% by day 7 of CR. Consistent with decreased sodium excretion was the drop in plasma ANP (from 82.4 +/- 4.3 to 68.0 +/- 5.8 pg/ml). To explore the possibility that CR lowers BP through an ANP receptor-dependent mechanism that is independent of its effect on sodium retention, we measured the cardiovascular parameters of mice deficient in the ANP receptor (NPR1(-/-)) or the ANP clearance receptor (NPR3(-/-)). Mean BP fell from 117.1 +/- 3.9 to 108.0 +/- 4.7 mmHg in the NPR1(-/-) mice and from 87.0 +/- 2.4 to 78.4 +/- 1.7 mmHg in the NPR3(-/-) mice during CR. These data indicate that the hypotension induced by CR does not depend on increased sodium excretion. Rather, it appears that the mouse responds to the low BP induced by CR with an increase in sodium reabsorption. Furthermore, circulating ANP levels and data from NPR1(-/-) and NPR3(-/-) mice suggest that the ANP pathway may not be involved in the cardiovascular response to CR.
Hunt
Lisa M
LM
Dept. of Biology, Williams College, Williamstown, MA 01267, USA.
Hogeland
Emily W
EW
Henry
Maria K
MK
Swoap
Steven J
SJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D001919:Bradycardia / Q000503:physiopathology*; D031204:Caloric Restriction; D003243:Consciousness; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D006339:Heart Rate / Q000502:physiology; D007022:Hypotension / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010275:Parasympathetic Nervous System / Q000502:physiology; D017461:Receptors, Atrial Natriuretic Factor / Q000378:metabolism*; D012492:Salts / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000502:physiology; D013686:Telemetry; D014882:Water-Electrolyte Balance / Q000502:physiology
D012492:Salts; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A; C073616:atrial natriuretic factor receptor C