-Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 min of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (n ϭ 13). The O&S increased limb circumference, MSNA burst rate (arm: ⌬6.7 Ϯ 0.7; leg: ⌬6.8 Ϯ 0.7 bursts/min), and total activity (arm: ⌬199 Ϯ 14; leg: ⌬172 Ϯ 22 units/min) and BP (arm: ⌬4.3 Ϯ 0.3; leg: ⌬9.4 Ϯ 1.4 mmHg) from the baseline. The MSNA and BP responses during arm O&S correlated with those during leg O&S. Occlusion alone had no effect on MSNA and BP. MSNA (r ϭ 0.607) responses during arm O&S correlated with those evoked by the saline infusion into the arm. These correlations suggest that sympathetic activation during limb O&S is likely, at least partially, to be evoked via the venous distension reflex. These data suggest that suction of an occluded limb evokes sympathetic activation and that the limb venous distension reflex exists in arms and legs of normal humans.autonomic; blood pressure regulation; vessel PRIOR STUDIES HAVE SHOWN THAT the distension of abdominal veins increases sympathetic efferent activity in rabbits (2) and dogs (12). Limb venous ligation evokes vasoconstriction in both the occluded and contralateral extremities in dogs (5). Evidence in animals suggests that afferent nerve endings in peripheral veins may sense regional blood volume changes and, in turn, contribute to the blood pressure (BP) regulation via a reflex response in cats (11, 21), rabbits (2), and dogs (12). Venous distension increases the discharge of group III and IV afferent nerves in cat hindlimbs (18).Our recent reports (7-10) have shown that volume infusion (saline or albumin solution, 5% forearm volume, ϳ50 ml) into the veins of an occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and BP in human subjects. The magnitude of the MSNA and BP responses depends on the volume and the rate of the infusate during arm vein distension (8). When lidocaine is added to the forearm infusate, the MSNA and BP responses to venous distension are abolished (9). These observations clearly suggest that limb venous distension evokes a sympathoexcitatory reflex (termed venous distension reflex) and, thus, increases BP in humans. Of note, a recent report by Yamauchi et al. (33) has shown this reflex is also present in rats. Additionally, we have shown that venous infusion of albumin evokes a larger and more sustained increase in MSNA and BP than those with infusion of equal vo...