Limb venous distension evokes sympathetic activation via stimulation of the limb afferents in humans

Abstract

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects.

Fig. 1.

Absolute value of cardiovascular variables and muscle sympathetic nerve activity (MSNA) in the saline and lidocaine trials. MAP, mean arterial blood pressure; HR, heart rate; WE, “W-E occlusion” procedure; Preinf, the last 3 min of the 4-min preinfusion period; Infus, the last 30 s of the infusion; P30s, 0–30 s of the postinfusion period; P60s, 30–60 s of the postinfusion period; P2m and P3m, the 2nd and 3rd min of the postinfusion period, respectively. P < 0.05 vs. baseline (*), vs. preinfusion (†), and vs. lidocaine trial (‡) (n = 6 subjects). No MSNA or MAP response was evoked in the lidocaine trial.

Fig. 2.

Absolute value of cardiovascular variables and MSNA in the saline and albumin trials. P < 0.05 vs. baseline (*), vs. preinfusion (†), and vs. saline trial (‡) (n = 11). Notice the sustained MSNA and MAP responses (at P60s) in the albumin trial.

Fig. 3.

Cardiovascular and MSNA responses in saline and albumin trials. The values are changes from the preinfusion to the Max period. *P < 0.05 (n = 11). Infusion of albumin evoked greater MSNA and MAP responses than infusion of the same volume of saline.

Fig. 4.

Representative tracing of MSNA and blood pressure during infusion of albumin solution (top), saline (middle), or lidocaine (90 mg) solution (bottom) in the venous circulation of an arterially occluded arm in one subject. The volume of the infusate in the 3 trials was equal to 5% forearm volume. Notice the clear MSNA activation and blood pressure increases during the infusion of saline or albumin solution while the responses were not evoked during the infusion of lidocaine solution.