Characterizing sympathetic neurovascular transduction in humans

Abstract

Despite its critical role for cardiovascular homeostasis in humans, only a few studies have directly probed the transduction of sympathetic nerve activity to regional vascular responses--sympathetic neurovascular transduction. Those that have variably relied on either vascular resistance or vascular conductance to quantify the responses. However, it remains unclear which approach would better reflect the physiology. We assessed the utility of both of these as well as an alternative approach in 21 healthy men. We recorded arterial pressure (Finapres), peroneal sympathetic nerve activity (microneurography), and popliteal blood flow (Doppler) during isometric handgrip exercise to fatigue. We quantified and compared transduction via the relation of sympathetic activity to resistance and to conductance and via an adaptation of Poiseuille's relation including pressure, sympathetic activity, and flow. The average relationship between sympathetic activity and resistance (or conductance) was good when assessed over 30-second averages (mean R(2) = 0.49±0.07) but lesser when incorporating beat-by-beat time lags (R(2) = 0.37±0.06). However, in a third of the subjects, these relations provided relatively weak estimates (R(2)<0.33). In contrast, the Poiseuille relation reflected vascular responses more accurately (R(2) = 0.77±0.03, >0.50 in 20 of 21 individuals), and provided reproducible estimates of transduction. The gain derived from the relation of resistance (but not conductance) was inversely related to transduction (R(2) = 0.37, p<0.05), but with a proportional bias. Thus, vascular resistance and conductance may not always be reliable surrogates for regional sympathetic neurovascular transduction, and assessment from a Poiseuille relation between pressure, sympathetic nerve activity, and flow may provide a better foundation to further explore differences in transduction in humans.

Figure 1. Schematic of the sympathetic neurovascular transduction assessment via an adaptation of Poiseuille’s relation between pressure, sympathetic activity, and flow.

We assume that pressure drives flow within the same beat, and fit blood pressure to flow (step 1). The estimated parameter (k) provides an estimate for the gain of blood pressure, analogous to admittance (i.e., the inverse of impedance). Subsequently, we fit sympathetic activity to the remaining residuals in flow (pressure-independent flow; step 2). The estimated parameters (c_t) provide values for the time course of regional neurovascular transduction while the total area under the transfer function between sympathetic activity and blood flow provides the regional sympathetic neurovascular transduction estimate (third panel).

Figure 2. Percent variance explained (R²) by different approaches to sympathetic neurovascular transduction.

Figure 3. Reproducibility of blood pressure gain and sympathetic neurovascular transduction assessed via the Poiseuille relation.

IHE 1 and IHE 2 denote separate isometric handgrip exercises. Each subject is denoted by a different symbol.

Figure 4. Relation between gain derived from resistance and gain derived from the Poiseuille relation between pressure, sympathetic activity, and flow.

Upper panel shows the relation between both gains (linear regression, R² = 0.37, p<0.05; bars show the standard error of the gain relations). Bottom panel shows the Bland-Altman assessment of agreement between the absolute magnitudes of both gains.

Figure 5. Gain relations between blood pressure and blood flow and between sympathetic activity and blood flow (sympathetic neurovascular transduction) assessed via the Poiseuille relation.

*p<0.05.

Figure 6. Time course of sympathetic effects.

*p<0.05.

Figure 7. Relation of sympathetic transduction to resting mean blood pressure and resting sympathetic activity.

Gray circles denote individuals >40 years of age, and white triangles denote individuals <30 years of age.