Altered heart rate regulation by the autonomic nervous system in mice lacking natriuretic peptide receptor C (NPR-C)

Figure 1. Incidence of sinus pauses in wildtype and NPR-C−/− mice. (A) Summary of differences in HR in conscious, unrestrained NPR-C+/+ and NPR-C−/− mice. (B) Representative telemetric ECG recording illustrating the occurrence of sinus pauses. (C) Summary data demonstrating the occurrence of sinus pauses in NPR-C+/+ and NPR-C−/− mice. (D) Summary data demonstrating the duration of sinus pauses in NPR-C+/+ and NPR-C−/− mice. *P < 0.05 vs NPR-C+/+ by Student’s t-test; n = 10 NPR-C+/+ and 10 NPR-C−/− mice.

Figure 2. Variability in RR interval in wildtype and NPR-C−/− mice. Representative RR-interval histograms generated from 24 hrs of telemetric ECG recording for NPR-C+/+ (A) and NPR-C−/− (B) mice respectively. Bin width is 10 ms. These data, which demonstrate a reduction in HR variability in NPR-C−/− mice, are representative of measurements made in 10 NPR-C+/+ and 10 NPR-C−/− mice.

Figure 3. Circadian changes in heart rate in wildtype and NPR-C−/− mice. Representative RR interval tachograms from 48 hrs of telemetric ECG recording in NPR-C+/+ (A) and NPR-C−/− (B) mice. (C) Summary data illustrating mean RR interval in NPR-C+/+ and NPR-C−/− mice during day and night cycles. *P < 0.05 using two-way ANOVA with a Holm-Sidak test; n = 10 NPR-C+/+ mice and 10 NPR-C−/− mice.

Figure 4. Differences in heart rate between wildtype and NPR-C−/− mice during high activity and low activity phases. (A) Representative plot illustrating locomotor activity signals measured in counts per minute (cpm). The gray regions are classified as low activity phases and the white regions are considered as high activity phases. (B) Summary of activity levels (averages during low and high activity phases) between wildtype and NPR-C−/− mice. Data analyzed using Student’s t-test. (C) Representative tachograms derived from 10 min sections of telemetric ECG recordings during low and high activity phases in NPR-C+/+ and NPR-C−/− mice. (D) Summary data illustrating the difference between RR interval during low and high activity phases in NPR-C+/+ and NPR-C−/− mice. *P < 0.05 by Student’s t-test; n = 10 NPR-C+/+ mice and 10 NPR-C−/− mice.

Figure 5. Assessment of HRV by time domain analysis in wildtype and NPR-C−/− mice during low and high activity phases. Summary data illustrating (A) the standard deviation of all RR intervals (SDNN), (B) the root mean square of the difference of successive RR intervals (RMSSD) and (C) the percentage of normal consecutive RR intervals differing by >6 ms (pNN6) in NPR-C+/+ and NPR-C−/− mice. *P < 0.05 vs. NPR-C+/+ within activity phase; + P < 0.05 vs low activity within genotype by two-way ANOVA with the Holm-Sidak posthoc test; n = 10 NPR-C+/+ mice and 10 NPR-C−/− mice.

Figure 6. Assessment of HRV (SDNN) in wildtye and NPR-C−/− mice after correcting for heart rate. (A) Plot of SDNN in NPR-C+/+ and NPR-C−/− mice in different conditions as a function of HR. Data were fit with an exponential function to correct for HR as detailed in the methods. (B) Linear regression analysis of uncorrected SDNN as a function of HR in NPR-C+/+ and NPR-C−/− mice (same mice as used in panel A). (C) Linear regression analysis of corrected SDNN as a function of HR in NPR-C+/+ and NPR-C−/− mice. Correlation coefficients in panels B and C obtained using Pearson’s correlation. (D) Summary data illustrating corrected SDNN in NPR-C+/+ and NPR-C−/− mice. *P < 0.05 vs. NPR-C+/+ within activity phase by two-way ANOVA with the Holm-Sidak posthoc test; n = 10 NPR-C+/+ mice and 10 NPR-C−/− mice.

Figure 7. Assessment of HRV by frequency domain analysis in wildtype and NPR-C−/− mice during high activity. Summary data illustrating total power of the HRV spectra (A), power in the HF band (B), power in the LF band (C), and the LF/HF ratio (D) in NPR-C+/+ and NPR-C−/− mice. *P < 0.05 vs. NPR-C+/+ by Student’s t-test; n = 10 NPR-C+/+ mice and 10 NPR-C−/− mice.

Figure 8. Effects of autonomic nervous system blockers on RR interval and frequency domain measures of HRV in wildtype and NPR-C−/− mice. Summary data illustrating the effects of atropine or propranolol on RR interval (A), total power of the HRV spectra (B), power in the high frequency band (C) and power in the low frequency band (D) in NPR-C+/+ and NPR-C−/− mice. *P < 0.05 vs. basal condition within genotype; + P < 0.05 vs. NPR-C+/+ within treatment condition by two-way repeated measures ANOVA with the Holm-Sidak posthoc test; n = 10 wildtype and 10 NPR-C−/− mice.