D uring static exercise, heart failure (HF) subjects activate the sympathetic nervous system differently than normal controls. HF causes metaboreceptor desensitization with either enhanced mechanoreceptor activity or central command. In this report, we examined whether increased muscle interstitial pressure, as seen in HF, augments other neural systems. We measured muscle sympathetic nerve activity (MSNA; peroneal nerve) in 10 normals during static exercise (40% maximal voluntary grip) and posthandgrip circulatory arrest (PHG-CA). This was repeated after venous congestion (VC; cuff inflation to 90 mmHg). VC increased forearm volume (plethysmography) by 4.7%. MSNA responses to exercise were greater after VC (150.5 +/- 41.8 vs. 317.3 +/- 69.9 arbitrary units; P < 0.01). However, MSNA responses during PHG-CA were not affected by VC, and 31P nuclear magnetic resonance (n = 5) demonstrated no effect of VC on pH or H2PO4-. Similar effects of VC on MSNA were noted after ischemic exercise (n = 7), excluding flow alterations as the explantation. VC probably sensitized mechanically sensitive afferents since MSNA during involuntary biceps contractions increased after VC (n = 6), and skin sympathetic nerve responses during handgrip, an index of central command, were not increased by VC (n = 6).