The aim of this study was to quantitate the density of nerve terminals as well as their synaptic vesicle population in the adventitia of saphenous (SV and SA) and brachial veins and arteries (BV and BA) obtained from rats maintained in a horizontal control or a tilted position. Adult animals were kept individually in tube-like cages in a 45 degrees head-up position. After 2 wk, both tilted and control animals were anesthetized, and the whole body was perfused with fixative solution at physiological pressure. Vessels segments were then excised for electron microscopy and immunohistochemistry. The nerve terminal density (NTD) of SA was 8.20 +/- 1.46 nerve terminals/100 microm(2) cross section of adventitia and that of SV was 4.53 +/- 0.61 nerve terminals/100 microm(2) cross section of adventitia in control rats. Tilting caused a significant increase in NTD of both SA (70%) and SV (52%). The synaptic microvesicle density (SyVD) was larger in SA than SV in control rats (30.48 +/- 4.41 vs. 13.38 +/- 2.61 synaptic vesicles/10 terminal sections), but tilting resulted in more pronounced changes in SyVD of SV (95%) than SA (54%). No significant changes in NTD and SyVD of BA were found after tilt (-3.6% relative to 4.99 +/- 0.33 compared with 0.4% relative to 24.89 +/- 3.7, respectively). Whereas NTD of BV exhibited a tendency to increase (3.73 +/- 0.86 vs. 2.31 +/- 0.29 nerve terminals/100 microm(2) cross section of adventitia), SyVD did not change significantly (18.96 +/- 2.74 vs. 22.85 +/- 3.17 synaptic vesicles/10 terminal sections). A large number of nerve terminals of all vessels were tyrosine hydroxylase immunoreactive (containing norepinephrine). These findings support the hypothesis that long-term gravitational load causes adaptive morphological and functional remodeling of sympathetic innervation in blood vessels of the extremities.