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.

Several long-term antigravity defense mechanisms are activated in the lower extremity veins and microvessels when an organism is exposed to chronic orthostatic load. These mechanisms involve acute pressure-induced myogenic response, counterregulatory K+ channels, functional and structural remodeling of sympathetic innervation, and vascular network properties.

Sex hormone depletion induces significant alterations in contractility of the saphenous vein, which could perturb venous capacitance function and distensibility. This effect has a potential role in the development of hypertension and venous varicosity, and these changes could possibly be prevented by HRT.

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...

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