Cardiovascular Disease: Heart Rate and Blood Pressure
Blood pressure measurements allow the identification of targets that, upon inhibition, lead to a reduction in blood pressure. Angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists are very successful drugs in the treatment of hypertension. Both knockouts have low blood pressure. Blood pressure is measured using a non-invasive computerized tail-cuff system, the Visitech Systems BP-2000 (Visitech Systems, Inc.; Apex, NC). First described by Krege et al., (1995) this technique has been validated by several studies in mice, including the analysis of specific knockouts affecting blood pressure such as that of the type 1A angiotensin II receptor gene (Ito et al., 1995; Oliver et al., 1998; Sugiyama et al., 2001). Ten measurements of blood pressure are made per day on each of 4 days for each animal evaluated. Results are recorded as the pooled average of 40 measurements.
Heart rate is measured via a noninvasive tail-cuff method for four days on the Visitech BP-2000 Blood Pressure Analysis System. Heart rate is measured ten times each day for four days. The four days are then averaged to obtain a mouse's conscious heart rate. Administration of propanolol, a beta adrenergic receptor antagonist (beta-blocker) that reduces heart rate in humans, has been used as a pharmacological benchmark for this assay in mice (unpublished results).
Displayed below is a sample graph of how systolic blood pressure observations are presented. In comprehensive phenotypic data packages graphs are interactive. Raw or calculated data and statistics can be seen by clicking on points in the graph.
Figure illustrates systolic blood pressure measures of male and female (left), male (center), and female (right) mutant mice. Blood pressure measures of wild type littermates (green circle), homozygous (red diamond), and recent historical wild type (purple line) mice are plotted against long-term historical values (± 2 standard deviations) for wild type animals (green shading). Recent wild type values are calculated from data collected within 60 days of current measures and long-term historical values are derived from data collected on more than 10,000 wild type mice.
Ito M, Oliverio MI, Mannon PJ, Best CF, Maeda N, Smithies O, Coffman TM. (1995) Regulation of blood pressure by the type 1A angiotensin II receptor gene, Proc Natl Acad Sci USA, 92:3521-3525.
Krege JH, Hodgin JB, Hagaman JR, Smithies O. (1995) A noninvasive computerized tail-cuff system for measuring blood pressure in mice, Hypertension, 25:1111-1115.
Oliver PM, John SW, Purdy KE, Kim R, Maeda N, Goy MF, Smithies O. (1998) Natriuretic peptide receptor 1 expression influences blood pressures of mice in a dose-dependent manner, Proc Natl Acad Sci USA, 95:2547-2551.
Sugiyama F, Churchill GA, Higgins DC, Johns C, Makaritsis KP, Gavras H, Paigen B. (2001) Concordance of murine quantitative trait loci for salt-induced hypertension with rat and human loci, Genomics, 71:70-77.