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Lower sympathetic transduction of blood pressure in uncontrolled hypertensives: physiological adaptation, methodological limitation, or both?

Journal of Human Hypertension volume 36, pages 423–424 (2022)Cite this article

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We read with interest the recent paper by Kobetic et al. [1] reporting that resting sympathetic transduction of diastolic blood pressure (BP) was lower in untreated hypertensives vs. normotensive controls. The authors interpreted this difference to represent a compensatory physiological adaptation in hypertensives (e.g., decreased adrenergic sensitivity) to combat the effects of chronic elevations in sympathetic activity. A second explanation not discussed is the potential methodological limitation of comparing sympathetic transduction of BP between groups with different resting MSNA burst frequency. Using burst-triggered signal-averaging techniques, we (and others) have found negative relationships between sympathetic transduction of BP and resting MSNA in young healthy males and females, such that individuals with higher MSNA burst frequency have lower sympathetic transduction of BP [2,3,4]. Although this relationship does not specify a methodological contribution, we determined subsequently that this relationship is driven largely by differences in the timing of an MSNA burst relative to cyclic oscillations in BP [5]. For example, if a MSNA burst occurs at a BP above the mean level, the sympathetic transduction response can appear to be a drop in BP (i.e., negative sympathetic transduction of BP). Individuals with higher resting MSNA have a greater number of bursts occurring at higher BP levels, resulting in a lower average sympathetic transduction of BP. In contrast, comparing the differences in BP responses following MSNA burst and non-burst cardiac cycles reveals no influence of the triggering BP level (i.e., a consistent sympathetic transduction response). Thus, examining only the peak BP response following signal-averaging of MSNA bursts may introduce measurement variability, depending on the characteristics of the study participants.

The method employed by Kobetic et al. to calculate sympathetic transduction of BP was developed by their group and is based on a linear regression of the MSNA burst area-diastolic BP relationship; but does not incorporate cardiac cycles without MSNA bursts [6]. In the original description, the authors acknowledged the analytical challenges of examining individuals with high MSNA and posited that their method would be less likely to be influenced by resting sympathetic activity [6], though this was not tested. In contrast, the present study observed a strong negative relationship between resting MSNA burst incidence and sympathetic transduction of diastolic BP [1], consistent with signal-averaging work [2,3,4]. Extracting the data (PlotDigitizer) from Fig. 4 A [1], we re-evaluated the results applying an ANCOVA analysis to adjust for resting MSNA burst incidence. The difference in sympathetic transduction of diastolic BP between hypertensive and normotensive men was diminished and not statistically significant (0.05 ± 0.05 vs. 0.10 ± 0.04; P = 0.09). It is possible that more MSNA bursts firing at a higher BP in hypertensives (a consequence of having higher sympathetic activity) could be associated with lower absolute BP values and reduce the slope of the linear regression. The observation of a hypertensive participant with a negative sympathetic transduction of BP, at minimum, suggests that the method is not solely capturing the consequences of a sympathetic vasoconstrictor burst. It is important to acknowledge that our re-analysis does not preclude the possibility that sympathetic transduction of BP may be lower in hypertensives even following adjustment of resting MSNA but would suggest the effect size is much smaller and requires a larger sample size to address. Of note, we were unable to extract MSNA burst frequency data, which represents the primary stimulus for mediating end-organ responses. Lastly, although the MSNA burst area-diastolic BP linear regression was described as sympathetic-vascular transduction, measures of vascular resistance or conductance were not assessed [1]. Thus, the current findings reflect only sympathetic transduction of BP.

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References

  1. Kobetic MD, Burchell AE, Ratcliffe LEK, Neumann S, Adams ZH, Nolan R, et al. Sympathetic-transduction in untreated hypertension. J Hum Hypertens. 2021;1–8. https://doi.org/10.1038/s41371-021-00578-5.

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Authors and Affiliations

  1. Department of Human Health and Nutritional Sciences, University of Guelph, Guelph, ON, Canada

    Massimo Nardone & Philip J. Millar

  2. Toronto General Research Institute, Toronto General Hospital, Toronto, ON, Canada

    Philip J. Millar

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  1. Massimo Nardone
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  2. Philip J. Millar
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MN and PJM both conceived the work, drafted and revised the paper, approved the final paper version, and agree to be accountable for all aspects of the work.

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Correspondence to Philip J. Millar.

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Nardone, M., Millar, P.J. Lower sympathetic transduction of blood pressure in uncontrolled hypertensives: physiological adaptation, methodological limitation, or both?. J Hum Hypertens 36, 423–424 (2022). https://doi.org/10.1038/s41371-021-00638-w

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