Neural control of blood pressure in women: differences according to age

Abstract

Purpose

The blood pressure “error signal” represents the difference between an individual’s mean diastolic blood pressure and the diastolic blood pressure at which 50% of cardiac cycles are associated with a muscle sympathetic nerve activity burst (the “T50”). In this study we evaluated whether T50 and the error signal related to the extent of change in blood pressure during autonomic blockade in young and older women, to study potential differences in sympathetic neural mechanisms regulating blood pressure before and after menopause.

Methods

We measured muscle sympathetic nerve activity and blood pressure in 12 premenopausal (25 ± 1 years) and 12 postmenopausal women (61 ± 2 years) before and during complete autonomic blockade with trimethaphan camsylate.

Results

At baseline, young women had a negative error signal (−8 ± 1 versus 2 ± 1 mmHg, p < 0.001; respectively) and lower muscle sympathetic nerve activity (15 ± 1 versus 33 ± 3 bursts/min, p < 0.001; respectively) than older women. The change in diastolic blood pressure after autonomic blockade was associated with baseline T50 in older women (r = −0.725, p = 0.008) but not in young women (r = −0.337, p = 0.29). Women with the most negative error signal had the lowest muscle sympathetic nerve activity in both groups (young: r = 0.886, p < 0.001; older: r = 0.870, p < 0.001).

Conclusions

Our results suggest that there are differences in baroreflex control of muscle sympathetic nerve activity between young and older women, using the T50 and error signal analysis. This approach provides further information on autonomic control of blood pressure in women.

Appendix

In the original description of baroreflex threshold diagrams, Wallin et al. [22] found that in subjects with cardiac arrhythmias the wide ranges of blood pressure variations resulted in an S-shaped relationship between occurrence of sympathetic bursts and DBP. To define the relationship statistically probit transformation was used, and then the data points fitted a straight line which was characterized in terms of the T50 point and the slope of the probit line. In contrast, when variations of blood pressure are small (as in sinus rhythm) and data points fall within the linear part of the threshold diagram, linear regression has generally been assumed to provide valid measures of T50 and slope. This approach has been used in several studies. If, however, subjects have high or low resting burst incidence the data points may belong to the curved parts of the S curve. In such cases linear regressions may lead to values for T50 and/or slope that differ from those obtained with the probit method (Fig. 6). Linear and probit analyses of baroreflex threshold curves have not been compared previously in a systematic way. Therefore, to clarify at which burst incidence levels discrepancies between the two methods may occur, we made such comparisons in a group of healthy subjects with burst incidences ranging from low to very high values.

Fig. 6

Data points indicating percentage heart beats associated with a sympathetic burst at different diastolic blood pressures (DBP) in subjects with resting burst incidences of 96 (a) and 22 (b). Baroreflex threshold curves based on linear (solid line) and probit (dashed line) analysis. Corresponding T50 values indicated by arrows

The material consists of 51 healthy normotensive subjects (33 men, 18 women), aged 21–71 years, MSNA burst incidence ranged between 16 and 97 bursts/100 heartbeats and burst frequency between 11 and 60 bursts/min. The differences between the results obtained with the two methods are summarized in Fig. 7. For T50 the results are more or less identical at burst incidence between 30 and 70 (Fig. 7a). At lower or higher burst incidences, however, differences start to occur, and for burst incidences above 80 or below 20 the differences are sometimes large. Also for the regression lines (Fig. 7b) differences between slopes are mostly small when burst incidences are between 30 and 70 but occasional exceptions do occur. Outside this range the differences increase and at high or low burst incidences they may be quite large.

Fig. 7

Difference between T50 values calculated with linear and probit methodology in subjects with different levels of resting muscle sympathetic nerve activity (MSNA) (a). For three subjects with burst incidences >80 the difference was >25 and therefore data points are not shown. Difference between slopes of threshold diagrams calculated with linear and probit methodology in subjects with different levels of resting MSNA (b)

The results confirm the supposition that for subjects with burst incidences in the medium range, linear and probit analyses of baroreflex threshold curves give similar results. If the subjects have a burst incidence range outside 30 to 70 bursts/100 heartbeats, however, linear analysis may result in erroneous values of T50 and slope (i.e., baroreflex sensitivity); only probit analysis provides reliable measures. Since MSNA burst incidence is known to increase with age [29], probit analysis should be the preferred method in most studies of age-related baroreflex control (like the present one). Special care is important when investigating patient groups with pathological increases of MSNA. A recent example is a study of patients with Takotsubo cardiomyopathy [30] in which linear regression analysis was used at burst incidences above 90; obviously in that case probit analysis would have been an adequate method. In addition, at burst incidences above 90 all data points may fall on the flat part of the S curve and, if so, baroreflex analysis of threshold curves becomes highly unreliable even with probit methodology.