RENIN ENHANCER KNOCKOUT MICE HAVE LOWER BLOOD PRESSURE AND LOCOMOTOR ACTIVITY BUT NORMAL BAROREFLEXES

摘要

Background: Previous studies have revealed that the promoter that controls renin expression is under the strong influence of a far (2.6 kb)-upstream enhancer. Mice have recently been generated with targeted deletion of the Ren-1~c enhancer (REKO mice) and which show a very low expression of renin (see separate abstract), hi the present study, we compared cardiovascular variables in REKO and wild-type (WT) mice to determine the importance of the renin gene enhancer in blood pressure regulation.Methods: Male C57BL6 (WT) and renin-enhancer knockout (REKO) mice (n = 8 per group) were implanted with telemetry devices (Datasciences TA11PA-C20) to monitor mean arterial pressure (MAP), heart rate (HR), and locomotor activity in the unrestrained state. Mice were randomly placed on high (3.1%), normal (0.4%) and low (0.05%) NaCl for a period of 2 weeks and the diet rotated for a total of 6 weeks of the study.Results: The average 24 hour MAP was 114 (+-) 1 mmHg for WT and 104 (+-) 1 mmHg for REKO mice on the normal salt diet (P < 0.001 for difference; n = 8 per group). HR was similar in the 2 groups, but locomotor activity was 41% lower in the REKO mice (P < 0.001). Day-night differences in MAP and HR were also similar in the 2 strains. A 3% high salt diet normalized MAP in the REKO mice, but had no effect in the WT mice. Blood pressure and HR variability, HR baroreflex sensitivity assessed by spectral analysis were similar in the 2 strains.