Earlier, substantial increases in the intramural sympathetic innervation density of rat hind-limb blood vessels were found after 2 weeks of experimental orthostasis with tubular 45° headup tilt cages. In the present study, we presumed that chronic head-down tilting induces opposite changes in the innervation density. Tilted rats were kept 45° head-down in long tubular cages for either 2 or 4 weeks (HDT2, HDT4), and the control animals were maintained in horizontal tilt cages for the same period (HOR2, HOR4). Segments of the saphenous and brachial veins and arteries were used for quantitative electron microscopic examinations. Intramural innervation density was defined by nerve terminal density (NTD) and synaptic microvesicle count (SVC) within the vascular Our previous work, applying a novel chronic 45°head-up tilt model of orthostasis [1,2], revealed several long-term vascular mechanisms supporting orthostatic tolerance in the hind limbs [3]. These mechanisms include an enhancement of the acute-pressure-induced myogenic response of saphenous vein with increases in smooth muscle cell count and in passive vessel diameter without much change in the wall thickness [1,[4][5][6]. Chronic head-up tilt also influences the microcirculatory network properties. A significant rarefaction of microvessels was found in the hind-limb oxidative skeletal muscles of rat after two weeks of orthostasis [7]. Branching angles decreased, and vessel diameters increased in the superficial venous system of the saphenous region of rats in response to long-term orthostasis [8]. The amount of electron-dense vesicles of ap- adventitia. Neither HDT2 nor HDT4 resulted in a decrease of NTD or SVC of the saphenous and brachial veins or arteries; instead, a tendency to increase was observed in some cases. Thus, in contrast to the large increases we found earlier in hind-limb vascular innervation density after 2 weeks of head-up tilting, head-down tilting of the same duration-or even twice as long-did not decrease the adventitial innervation density in our model. We assume that the quasi-free locomotor exercise the tilted animals in the long tubular cages were allowed may counteract a possible suppressive effect of chronic head-down tilt on hind-limb vascular innervation density. [The Japanese Journal of Physiology 55: [127][128][129][130][131][132][133][134] 2005] Key words: brachial vein, head-down tilt, saphenous artery, saphenous vein, vascular innervation.proximately 0.1-0.2 µm diameter (which we identified in the endothelium cells of rat saphenous vein) greatly decreased during two weeks of orthostatic body position [9,10].After 2 weeks of 45° head-tilting, among the most interesting observations we made in this model of orthostasis was a surprisingly large increase (nearly double) in the adventitial (intramural) sympathetic innervation density of hind-limb blood vessels, especially the veins [2]. This increase included both the density of nerve terminals (NTD) and the number of synaptic microvesicles in the terminals (SVC). The...