Respiratory modulation of muscle sympathetic nerve activity is not increased in essential hypertension or chronic obstructive pulmonary disease

Abstract

We examined cardiac and respiratory modulation of muscle sympathetic nerve activity (MSNA) in 13 patients with essential hypertension (HT) and 15 with chronic obstructive pulmonary disease (COPD), and compared these with a group of young healthy controls (YHC) and older healthy controls (OHC). There were no significant differences in age of the OHC and HT subjects. MSNA was recorded via a tungsten microelectrode inserted percutaneously into the common peroneal nerve. Respiration was recorded by a strain-gauge transducer around the chest and ECG recorded by surface electrodes. Cardiac and respiratory modulation of MSNA was quantified by fitting polynomials to the cross-correlation histograms constructed between the sympathetic spikes and ECG or respiration. Cardiac modulation was high across all groups, but was significantly lower in COPD (75.9 ± 4.4%) than in the HT (92.4 ± 3.0%), OHC (93.7 ± 1.3%) or YHC (89.1 ± 1.6%) groups. Across all groups, respiratory modulation was significantly lower than cardiac modulation. Respiratory modulation in HT (45.2 ± 5.7%) and COPD (37.5 ± 6.3%) was not higher than in the OHC (47.2 ± 5.4%) or YHC (49.5 ± 6.0%) groups. We have shown that respiratory modulation of MSNA is present in all groups, is consistently lower than the magnitude of cardiac modulation, and is not increased in HT or COPD, arguing against an amplified respiratory-sympathetic coupling in hypertension. Moreover, given that patients with COPD are chronically asphyxic, these data indicate that an increased chemical drive does not increase respiratory modulation of MSNA.

Figure 1. Multi-unit recording of muscle sympathetic nerve activity from a 45-year-old normotensive female subject

The mean-voltage neurogram is shown in the RMS-nerve trace; this was used to quantify the number of sympathetic bursts. Note that bursts of MSNA occurred in many, but not all, cardiac intervals in this subject. Discriminated spikes extracted from the nerve recording are illustrated as standard pulses (spikes). The times of occurrence of each heart beat (R-waves) and peaks of each breath (insp. peaks) are also shown as standard pulses. These timing events were used to generate the cross-correlation and auto-correlation histograms.

Figure 2. Multi-unit recording of muscle sympathetic nerve activity in a 64-year-old hypertensive female subject

The mean-voltage neurogram is shown in the RMS-nerve trace. Note that bursts of MSNA occurred in most cardiac intervals in this subject, and that overall levels of MSNA were higher than in the control subject shown in Fig. 1.

Figure 3. Cross-correlation histograms (upper traces in each panel) and auto-correlation histograms (lower traces in each panel) between sympathetic spikes and respiration (A) and ECG (B)

Data obtained from the same subject illustrated in Fig. 1. Smoothed polynomials (thick lines) have been fitted to the histograms. The numbers on the y-axis refer to the numbers of spikes per 50 ms bin. Time zero, corresponding to the triggering event in the cross- or auto-correlograms, is indicated by the vertical dashed lines.

Figure 4. Mean cardiac and respiratory modulation indices across the four groups studied

YHC, young healthy control (n = 12); OHC, older healthy control (n = 10); HT, patients with essential hypertension (n = 13); COPD, patients with chronic obstructive pulmonary disease (n = 15). Across groups, cardiac modulation indices were consistently higher than the respiratory modulation indices. Relative to the value in the OHC group, cardiac modulation was significantly lower in COPD; **P < 0.01.