Exercising Restraint in Measuring Blood Pressure in Conscious Mice

Abstract

A rat's tail is a slender appendage on which the weight of so much research in hypertension hangs, yet blood pressure measurements recorded from it are usually taken for granted, often abused, but seldom discussed," observed Buang in an earlier commentary. 1 The same methodology has now been adapted to mice. Restraining the animals is a serious problem. A 7-day training period is recommended to accustom the animals to the restrainers. [2][3][4] Nevertheless, heart rates recorded while mice are in a restrainer are higher than those in the resting state. 3 Furthermore, blood pressures also appear to be higher, even though coaxing the animals into restrainers becomes easier day-to-day. 5 A blood pressure-elevating effect of restrainers has been observed in the rat. 6 Telemetric blood pressure and heart rate solves this problem. 6 We made telemetric measurements of blood pressure and heart rate on four 129Sv/J mice outfitted with telemetry as described earlier. 7 The purpose of our observations was to test the notion that "conditioning" might lessen the effects of restraint on blood pressure and heart rate. After an initial 120-minute control period, the mice were placed for 30 minutes in a 25-mm wide, 110-mm long lucite restrainer. Thereafter blood pressure and heart rate were recorded for an additional 120 minutes. We made daily recordings, 10 recordings for each mouse during 2 weeks. To judge the influence of restraint, we used the heart rate (HR) and the mean arterial pressure (MAP). In mice, tail-cuff pressure correlates well with MAP, according to earlier reports. 2,3 Data (meanϮSEM) were analyzed with the one-way ANOVA and t tests with the Bonferroni correction. The experimental protocol was approved by the local council on animal care, whose standards correspond to those of the American Physiological Society. Figure 1 shows HR and systolic (SBP) and diastolic blood pressures (DBP) from a representative mouse during the first restraint and the tenth restraint. The responses do not appear different. At the first restraint, SBP increased to 148 mm Hg, DBP to 113 mm Hg, and HR to 754 beats/ min. In the second week, at the tenth restraint, the responses to the restrainer were similar. Figure 2 shows that MAP measured under control conditions for 4 mice was stable throughout the 2-week recording period and averaged 102Ϯ8 mm Hg in the first week and 100Ϯ7 mm Hg in the second week. The corresponding basal HR values were 522Ϯ11 beats/min in the first week and 483Ϯ9 beats/min in the second week. No "conditioning" was observed for either MAP or HR when comparing the sessions of the first week with the sessions of the second week (PϭNS). Two hours after restraint, blood pressure and heart rate returned to basal levels in the mice.We conclude that blood pressure and heart rate increases are similar during restraining, independent of "conditioning" over 10 days. The data were convincing to the point that 4 mice were sufficient to illustrate the problem, so we did not study more. The results indicate that both blood pressu...

Tail‐Cuff Technique and Its Influence on Central Blood Pressure in the Mouse

“…We observed ≈33% and 44% increase in blood pressure and heart rate throughout this period, respectively. Other researchers show similar changes in mice24 and rats 37, 38. Although other biomarkers of stress are not addressed in this study, there is a wealth of evidence on this subject,11, 12 which also support our observation that stress markers remain elevated throughout the period of restraint and show a trend to increase if the restraint period is increased 12…”

“…It is believed that the mice habituate to the tail‐cuff procedure following repeated exposure and there is a common practice to “train” mice before starting an experiment 10, 21, 22. However, there is evidence that this does not happen 23, 24. Moreover, the tail‐cuff technique has been used to model stress that was defined by measuring heart rate 23…”

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

“…This value was the systolic pressure for that day. Although tailcuff plethysmography underestimates absolute blood pressure values (19), this does not compromise our experiments since relative comparisons are made within groups of animals. After 7 days blood pressure was measured, and rats were then sacrificed in preparation for immunocytochemistry.…”

Response to genetic manipulations of liver angiotensinogen in the physiological range

“…Part of this apparent discrepancy may reflect an intrinsic difference in the method used for blood pressure measurements. Basal differences may be magnified by the stress associated with the restraint necessary to perform tail-cuff measurements (Gross and Luft 2003). This effect could result either from direct vasoconstriction or from a transient increase in A-II formation induced by acute renin release, amplifying differences in circulating plasma AGT, so long these remain below the K m of the reaction, as clearly would be the case in the adipose overexpression model.…”