Submitted on April 13, 2004
Accepted on June 7, 2004
Hypotension and bradycardia during caloric restriction in mice are independent of salt balance and do not require the ANP receptor
Lisa M. Hunt1, Emily W. Hogeland1, Maria K. Henry1, and Steven J. Swoap1*
1 Department of Biology, Williams College, Williamstown, MA, USA
* To whom correspondence should be addressed. E-mail: sswoap{at}williams.edu.
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, cardiovascular parameters of c57/Bl mice were measured with radiotelemetry while collecting urine. 23-hour mean BP dropped from
108.6 ± 1.8 to 92.7 ± 2.4 mmHg, and 23-hour HR dropped from 624 ± 5 to 426 ± 13 bpm over 7 days of CR at 29 °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 blood pressure induced by CR with an increase in sodium reabsorption. Further, circulating ANP levels and data from NPR1-/- and NPR3-/- mice suggest that the ANP pathway may not be involved in the
cardiovascular response to caloric restriction.
