Chronic administration of quercetin induces biomechanical and pharmacological remodeling in the rat coronary arteries.

Acute dilation brought about by the dietary flavonoid quercetin in coronary arterioles has been described earlier, but no information is available on its chronic effects. Male Wistar rats (body weight about 190 g) were divided to two groups: the quercetin-treated group (n=22) had quercetin supplementation of approximately 30 mg/kg/day, whereas the control group (n=20) had none. After eight weeks of treatment, intramural coronary arterioles with identical passive diameters (178+/-14 microm and 171+/-9 microm) were prepared and their biomechanics and pharmacological reactivities were tested using pressure arteriography ex vivo. The spontaneous tone of quercetin-treated arteries was higher (16.5+/-1.9 % vs. 12.9+/-0.9 %), which resulted in a reduced lumen size (144+/-9 microm vs. 167+/-12 microm), thicker vascular wall (22.6+/-1.8 microm vs. 17.4+/-1.6 microm) and decreased tangential wall stress (16.8+/-1.1 kPa vs. 20.5+/-1.6 kPa) in supplemented animals (in spontaneous tone at 50 mm Hg, p<0.01 in all these comparisons). Elevated basal NO release resulted in increased endothelial dilation in quercetin-treated animals, especially at higher intraluminal pressures (10.8+/-2.5 % vs. 5.7+/-1.3 % at 70 mm Hg, p<0.01). We found remodeling of the geometry of coronary arterioles to ensure higher dilatory reserve and nitrogen monoxide production, as well as lowered elastic stress of the vessel wall.

A simple standard technique for labyrinthectomy in the rat: A methodical communication with a detailed description of the surgical process.

Aims Labyrinthectomized rats are suitable models to test consequences of vestibular lesion and are widely used to study neural plasticity. We describe a combined microsurgical-chemical technique that can be routinely performed with minimum damage. Methods Caudal leaflet of the parotis is elevated. The tendinous fascia covering the bulla is opened frontally from the sternomastoid muscle's tendon while sparing facial nerve branches. A 4 mm diameter hole is drilled into the bulla's hind lower lateral wall to open the common (in rodents) mastoid-tympanic cavity. The cochlear crista (promontory) at the lower posterior part of its medial wall is identified as a bony prominence. A 1 mm diameter hole is drilled into its lower part. The perilymphatic/endolymphatic fluids with tissue debris of the Corti organ are suctioned. Ethanol is injected into the hole. Finally, 10 µL of sodium arsenite solution (50 µM/mL) is pumped into the labyrinth and left in place for 15 min. Simple closure in two layers (fascia and skin) is sufficient. Results and conclusion All rats had neurological symptoms specific for labyrinthectomy (muscle tone, body position, rotatory movements, nystagmus, central deafness). Otherwise, their behavior was unaffected, drinking and eating normally. After a few days, they learned to balance relying on visual and somatic stimuli (neuroplasticity).

Regional differences in statistical geometry of endothelial dense granules in human extremity veins.

OBJECTIVES: Leg and arm human veins are exposed to different gravitational stresses. We investigated if there is difference in the amount and geometry of secretory vesicles in their endothelium. METHODS: Superficial small vein segments were removed during vascular operations for electromicroscopic analysis. Vesicular area/total endothelial cross-sectional area was determined by computer-based morphometry. Long and short axes of granule cross sections were measured by image analyzing software. RESULTS: Vesicular density in all samples was 2.26 ± 0.34%. There was no significant difference between the vesicular densities of upper extremity and leg. The shape of the vesicles was more frequently elongated in leg than in arm sections (p < 0.01). CONCLUSIONS: The density of the vesicles does not depend on vascular region or orthostatic load. Ellipticity of these granules is significantly different in areas exposed to different gravitational stresses. This might contribute to the differences of thrombotic and hemodynamic properties of leg and upper body veins.

Comparison of passive and active biomechanical properties of human cervical and leg veins.

AIM: The aim of this study was to evaluate and compare passive and active biomechanical properties of human superficial veins exposed in vivo to different orthostatic stresses. METHODS: Superficial veins from jugular and saphenous regions were studied (11 segments each). Digitalized pressure-diameter curves were recorded in Krebs-Ringer solution, and after administration of 10-5M norepinephrine and 10-5M acetylcholine. Calcium-free solution was used to determine passive biomechanical properties. Similar tissue samples were collected for histochemistry. Resorcin-fuchsin stainings and immuno-histochemistry for smooth muscle actin were used. RESULTS: The outer radius of the relaxed samples was identical. Leg vein walls were thicker in Krebs-Ringer solution (110 ± 11 vs. 84 ± 7 µm at 30 mmHg). Isobaric wall stress was significantly higher in cervical veins. The significant differences in incremental distensibilities and elastic moduli were dependent on pressure level and smooth muscle tone. Spontaneous tone and norepinephrine induced contractions were significantly higher in leg veins (at 30 mmHg 18.3 ± 4.1 vs. 5.6 ± 1.8% and 37.6 ± 4.5 vs. 11.2 ± 4.3 %, respectively). Endothelial dilation was larger in cervical vein segments (3.8 ± 0.9% vs. 1.8 ± 0.5%). Resorcin-fuchsin and smooth muscle actin staining structures were more abundant in leg veins. CONCLUSION: Comparing active and passive biomechanical properties of human veins affected chronically by different orthostatic loading, we found several quantitative differences that reflect the physiological adaptation mechanisms to long-term gravitational stress.

Determination of venous blood flow velocity using digital videomicroscopy (A short methodical communication).

BACKGROUND/AIM: There is a limited number of methods to measure blood flow velocity in small veins. A cheap and simple new videomicroscopic method developed in our laboratories is described in the paper. METHODS: A stretch of the saphenous vein of the rat was exposed by careful micropreparation on the thigh of anesthetized animals. Bolus amount (approx. 5 µl) of saline was infused into a small side branch through a microcannula to dilute flowing blood. Videomicroscopic picture of the vein was then taken of the exposed upstream stretch of the vein. Serial pictures were digitized and analyzed using macro functions of the Image J software. Sensitive areas of serial pictures were selected and fitted. Consecutive pictures were subtracted from each other to better characterize their alteration in-between frames. Greyscale intensity values measured at different points of the inner diameter were averaged for each point of the vessel axis. Cross-correlations along the axis were then computed for consecutive frames with delays of 40, 80, 120 and 160 msec. Pixel offsets producing cross-correlation maxima were determined and used to compute mean flow velocity. RESULTS: Combination of digital subtraction and cross-correlation computations yielded easily identifiable maximums. Mean flow velocities could be determined with limited uncertainty. CONCLUSION: The described technique gives a cheap, simple and reproducible mean to determine mean blood flow velocities in small veins in anesthetized animals, where other current techniques (ultrasonography, laser-Doppler, fluorescently labelled red cell movement) are either expensive or can be applied with difficulty only.

Biomechanics and vasoreactivity of female intramural coronaries in angiotensin II induced hypertension.

Hypertension causes small vessel remodeling, vasomotor alterations. We investigated diameter, tone and mechanics of intramural small coronaries of female rats that received chronic angiotensin treatment to induce hypertension.Angiotensin II infusion (AII, 100 ng/bwkg/min, sc.) was used to establish hypertension in 10 female rats. Other 10 rats served as controls. Following 4 weeks of treatment, side branches of the left anterior descendant coronary (diameter approximately 200 microm) were isolated, cannulated and pressure-diameter curves were registered between 2-90 mmHg. Changes in vessel diameter were measured in Krebs solution, in the presence of thromboxane A2 receptor agonist (U46619, 10(-6) M), bradykinin (BK, 10(-6) M), and finally at complete relaxation (in Ca2+-free solution). Chronic AII treatment raised the mean arterial pressure (130+/-5 mmHg vs. 96+/-2 mmHg, average +/-SEM) significantly. Wall thickness of the AII group was significantly greater (40.2+/-4.2 microm vs. 31.4+/-2.7 microm at 50 mmHg in Ca2+ -free solution), but cross-section of the vessel wall did not differ. Tangentional wall stress and elastic modulus decreased significantly in hypertensive animals. Constrictions in the presence of U46619 were greater in the AII group (24.4+/- 5.6% vs. 14.5+/-3.3% at 50 mmHg). In hypertension, intramural small coronaries showed inward eutrophic remodeling, as a morphological adaptation following AII treatment enhanced thromboxane A2-induced tone.

Maintained geometry, elasticity and contractility of human saphenous vein segments stored in a complex tissue culture medium.

OBJECTIVE: Improved maintenance of endothelial function and higher viability of saphenous vein grafts stored in a complex tissue culture medium (TCM) have been demonstrated. This article studies the biomechanical properties of saphenous vein segments. DESIGN: Biomechanical properties of 72 saphenous vein segments remaining from coronary bypass grafting of 32 patients have been studied after different storage procedures. MATERIALS: The materials studied included fresh segments, segments stored in a cooled conventional physiological salt solution (normal Krebs-Ringer (nKR)) for 1-2 weeks, segments stored in a cooled chemically defined TCM (X-Vivo) for 1,2,3 and 4 weeks and segments cryopreserved for a few weeks. METHODS: Specimens were cannulated at both ends and pressure-diameter curves were recorded in the 0-85-mmHg range in nKR with 10 microM norepinephrine added to induce maximum smooth muscle contraction, as well as in Ca(2+)-free medium to induce full relaxation. Tensile strength was checked at 300 mmHg. Distensibility, elastic modulus and active strain were computed. RESULTS: Segments stored in nKR dilated morphologically, their distensibility decreased and they lost their ability to contract (1.5+/-0.7% from 10.1+/-1.5% of control) in 1 week. The TCM-stored segments preserved their contractility until 1 week, and this parameter only slowly decreased afterwards (first week, 11.5+/-7.3%; fourth week, 3.9+/-0.6%). There was a slight decrease in wall thickness but the lumen diameter was not affected. The elastic parameters of these segments were practically identical to those of fresh segments. Cryopreserved segments narrowed morphologically, their wall thickened and contractility diminished. CONCLUSIONS: Storage in TCM helps preserve the passive and active biomechanical properties of human saphenous vein segments. Such properties can be expected to improve graft tissue viability.

Vestibular control of intermediate- and long-term cardiovascular responses to experimental orthostasis.

Sustained orthostasis elicits the elevation of arterial blood pressure (BP) via sympathetic activation in conscious Wistar rats for at least 2 hours. We tested the hypothesis whether vestibular apparatus plays a role in BP and heart rate (HR) control in response to prolonged gravitational stress. BP and HR responses to 45 degrees head-up for either 2 or 24 hours were monitored by telemetry. Vestibular lesions (VL) were performed by a modified microsurgical-chemical technique. Horizontal BP and HR were not influenced by VL preceding 2-hour tilt. VL abolished the sustained 2-hour BP response to head-up tilt (8.3+/-0.9 mm Hg relative to horizontal values) while suppressed HR transiently only. VL eliminated diurnal BP fluctuations and decreased HR in horizontal position for 24 hours. Head-up tilt for 24 hours increased BP and HR progressively in intact animals, raising their daily average value by 5.6+/-0.7 mm Hg and 22.2+/-6 BPM, respectively. VL resulted in an initial BP rise followed by progressive BP reduction in response to long-term head-up tilt (4+/-2.2 mm Hg) without eliminating the tachycardia (34.4+/-5.4 BPM). Thus, blockade of labyrinthine inputs attenuates the BP responses elicited by both intermediate and long-term gravitational stress of orthostatic type. However, other sensory inputs derived from non-vestibular cues (e.g. proprioceptive, visual, visceral, cutaneous etc.) seem to be effective enough to maintain BP normal.

Generalized alterations in the biomechanical properties of large veins in non-thrombotic thrombophilic young patients.

AIM: In young, post-thrombotic patients, venous distensibility is decreased not only in the affected lower limb, but also in the contralateral limb and in the jugular vein when compared to age-matched control subjects. In the present study, we investigated venous wall mechanical properties in young, asymptomatic thrombophilic patients. METHODS: Eleven young (24+/-0.4 years) control subjects and 9 age-matched patients (21.1+/-1.8 years) with proven thrombophilic molecular defects, but without any signs or history of previous deep vein thrombosis, were compared. Anterolateral and mediolateral diameters of the common femoral, axillary and internal jugular veins were measured by ultrasonography in situ. Pressure alterations were induced by altering body positions and by pressure-controlled Valsalva tests. Distensibility was calculated from diameter and pressure changes. RESULTS: In thrombophilic patients, resting diameter of both the common femoral and of internal jugular veins at low transmural pressure was larger than those for the control subjects. Distensibility, however, was significantly less when high pressures were applied. Alterations in diameter of the axillary vein were minimal. CONCLUSION: Our measurements suggest that there are generalized changes in venous mechanical properties in thrombophilic patients even before the appearance of thrombotic processes. These biomechanical alterations of the venous wall and/or surrounding connective tissue are similar to those found in connection with aging and in post-thrombotic patients. The pathological mechanisms behind these processes are unknown.

Increased diameter and enhanced myogenic response of saphenous vein induced by two-week experimental orthostasis are reversible.

Previously, increased diameter and enhanced myogenic tone were seen after 2-week 45o head-up (HUT2) in the rat. We studied the reversibility and the effect of extended tilt on this phenomenon using two experimental groups: HUT2 plus 2-week horizontal (HUT2HOR2), and 4-week tilting (HUT4). 4-weeks in normal cages (NC4) served as control. Diameter of saphenous vein (SV) in 2-20 mm Hg pressure range, wall and media thickness, endothelial and smooth muscle cell densities, and cell proliferation were measured. The diameter of SV from HUT4 was significantly larger compared with HUT2HOR2 or NC4 within the whole pressure range both in Krebs-Ringer (870.4+/-21.3 vs. 778.2+/-24.9 and 771.6+/-28.1 microm at 10 mm Hg, respectively) and in Ca(2+)-free solution. Myogenic and norepinephrine-induced vascular tone, wall and media thickness did not differ among the three groups. Endothelial cell density decreased in HUT4 (10.7+/-1.2) vs. HUT2HOR2 (15.1+/-1.0) and NC4 (15.3+/-0.6), while that of smooth muscle was unchanged. No cell proliferation marker was seen. In conclusion, both increased diameter and enhanced myogenic tone of SV seen in HUT2 proved to be reversible. HUT4 resulted in increased SV diameter, similarly to HUT2, however, vascular tone was not amplified. This suggests that a prolonged orthostatic load may readjust the function of smooth muscle.

Nitric oxide modulates the interaction of pressure-induced wall mechanics and myogenic response of rat intramural coronary arterioles.

Interactions between the biomechanical characteristics and pressure-induced active response of coronary microvessels are still not well known. We tested the hypothesis that pressure-dependent biomechanical characteristics of the coronary vascular wall are modulated by the active myogenic response and local vasodilators. We have utilized data obtained previously in isolated rat intramural coronary arterioles (approximately 100 microm in diameter), in which the diameter was investigated as a function of intraluminal pressure (Szekeres et al.: J. Cardiovasc. Pharmacol., 43, 242-249, 2004). To characterize the magnitude of myogenic response, diameter was expressed as percent of passive diameter as a function of pressure (normalized diameter; ND). In addition, circumferential wall stress (WS) and incremental distensibility (ID) were calculated. In control conditions, after an initial increase between 0-30 mm Hg, ND decreased substantially as pressure increased from 30 to 150 mm Hg. Correspondingly, WS gradually increased as a function of pressure (from 0.3 +/- 0.03 to 34.7 +/- 4.4 kPa) exhibiting a plateau phase between 40-80 mm Hg. In contrast, ID decreased and reached negative values (min: -104.9 +/- 21.9 10(-6) m2/N at 50 mm Hg). Inhibition of nitric oxide (NO) synthase by L-NNA decreased basal diameter (approximately 35% at 2 mm Hg), eliminated pressure-induced changes in ND, reduced the slope of pressure-WS curve, and decreased ID at lower pressures. Simultaneous administration of L-NNA and adenosine (which restored initial diameter, i.e. length of smooth muscle) restored--in part--the pressure-induced reduction in ND, reversed the pressure-induced behavior of WS to control, but not that of ID. These results not only confirm that in coronary arterioles wall stress is regulated by the myogenic response, but also suggest that there is interplay between the mechanical behavior of the wall and the myogenic response. Furthermore, the presence of NO seems to be necessary for maintaining a higher distensibility of intramural coronary arterioles allowing increases in diameter to lower pressures, which then activate the myogenic mechanism resulting in constrictions and full development of myogenic tone, as indicated by the presence of negative slope of pressure-diameter curve in the presence of NO.

Does chronic experimental head-down tilt alter intramural innervation density of limb blood vessels?

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 degrees head-up 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 degrees 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 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.

Remodeling of the rat saphenous vein network in response to long-term gravitational load.

Our main objective was to test whether chronic orthostatic body position induces network changes in the saphenous vein superficial tributary system of the rat. Fourteen male Sprague-Dawley rats were kept in tilted tube cages (45-degree head-up position) for two weeks to induce chronic gravitational load to their leg veins. Ten animals housed in normal cages and four animals kept in horizontally positioned tube cages served as controls. The whole superficial network of the left saphenous vein was microprepared surgically under anesthesia, superfused with saline and observed under a videomicroscope, while normal flow and pressure were maintained in the lumen. Branching angles, lengths of venous segments and their diameters were measured offline from digitized images using special image-analyzing software. Several branching angles at the popliteal confluence were significantly reduced by 12.5-15.8 %. The in vivo diameter of the main branch (936+/-34 vs. 805+/-44 microm) and of one of the popliteal tributaries (776+/-38 vs. 635+/-36 microm) increased (p<0.05), comparing vessels from tilted animals with those from normal controls. Maintaining the animals in horizontal tube cages did not induce the above alterations. The increased diameters and reduced branching angles of the saphenous vein network observed are adaptive responses of the venous network to a long-term gravitational load.

Pharmacologic inhomogeneity between the reactivity of intramural coronary arteries and arterioles.

We hypothesized that because of their size, anatomic location, and hemodynamic function, coronary arteries and arterioles would respond differently to vasoactive substances. Intramural arteries (281.7 +/- 23.1 microm) and arterioles (77.3 +/- 6.6 microm) of the left anterior descending coronary of rats were isolated and cannulated. Spontaneous tone was lower in arteries than in arterioles (81.1 +/- 5.7 vs. 53.0 +/- 3.9% of passive diameter, p < 0.05 at 60 mm Hg intraluminal pressure). Arterial tone was adjusted by the thromboxane receptor agonist U46619 (5 x 10(-8) M ) to reach an active tone close to that of arterioles. Bradykinin elicited dilations in both types of vessels. Acetylcholine (10(-6) - 10(-5) M ) dilated arteries (by 42.6 +/- 11.5 microm) but constricted arterioles (by 16.4 +/- 9.3 microm). Sodium nitroprusside and adenosine elicited significantly greater dilations in arterioles than in arteries (by 7.9 and 11.9%, respectively, p < 0.05), whereas dilations to norepinephrine were similar. Inhibition of nitric oxide synthesis caused a significantly smaller constriction in arteries (10.2 +/- 3.31%) than in arterioles (31.6 +/- 6.9%) and completely blocked bradykinin-and acetylcholine-induced dilations, whereas it did not affect dilations to sodium nitroprusside, adenosine, and norepinephrine. Compared with arteries, arterioles have a greater spontaneous tone and enhanced nitric oxide modulation of basal tone and exhibit greater responsiveness to nitric oxide and adenosine. In addition, nitric oxide synthase is activated differently by pharmacologic stimuli in these segments. The qualitative and quantitative differences among vasoactive responses of coronary arteries and arterioles demonstrated in this study suggest segment-specific roles for endothelial and metabolic factors in regulation of coronary vascular resistance.

Acute, nongenomic vasodilatory action of estradiol is attenuated by chronic estradiol treatment.

Deficiency of estradiol or chronic estrogen treatment may alter the responses to this hormone in many tissues. A possible interaction between the acute nongenomic and the chronic effects of estradiol on microvessels have not been investigated yet. In the present study we have investigated whether acute in vitro vasodilatory action of estradiol on a small artery is altered by chronic estradiol pretreatment. Female rats were surgically ovariectomized and subjected to either estradiol replacement therapy (estradiol propionate, 450 micrograms/kg/week) or vehicle administration for 5 weeks. Cylindrical segments of the saphenous artery were studied using videocomputerized microarteriography in vitro. Estradiol, in concentrations of 10(-6) to 10(-4) M relaxed norepinephrine precontracted vessel segments in a dose-dependent manner. Magnitude of relaxation observed in arteries of estradiol replaced animals was significantly smaller at all concentrations than that of nonreplaced ovariectomized rats; maximal relaxation in the control ovariectomized group was 64.5% +/- 3.6%, while it was 34.3% +/- 4.2% only in the ovariectomized and estradiol replaced group (P < 0.001). Comparison of acute relaxations in response to papaverine and nifedipine failed to prove a reduced activity of the general relaxation machinery in estradiol replaced animals. We conclude that chronic estradiol replacement can downregulate the acute nongenomic vasorelaxation effect of this hormone in small arteries of ovariectomized rats.

Sex hormone replacement therapy reverses decreased venous distensibility in pharmacologically ovariectomized rats.

OBJECTIVE: To test the effect of female sex hormone depletion and replacement on the distensibility and geometry of the saphenous vein in female rats. DESIGN: Twenty Sprague-Dawley rats were pharmacologically ovariectomized by triptorelin. Ten of these animals received combined hormone replacement with estradiol and medroxyprogesterone acetate. The rest were given vehicle. Ten animals kept parallel without pharmacological ovariectomy served as controls. After 3 months of treatment, a segment of the saphenous vein was dissected. Pressure-diameter curves were recorded in relaxed, contracted, and control states using a microangiograph. RESULTS: Pharmacological ovariectomy lowered venous wall distensibility measured in contraction (at P=8 mm Hg: 4.41+/-1.21*10(-3) m2/N vs. control: 0.79+/-0.14*10(-3) m2/N; p < 0.05). Hormone replacement partially restored this value (1.8+/-0.49*10(-3) m2/N). No alterations in distensibility were found in the relaxed state. After adjusting for body weight, we found that pharmacological ovariectomy lowered venous inner radius significantly compared with control (p < 0.05), whereas hormone replacement increased it compared with pharmacological ovariectomy (p < 0.05) and more significantly compared with control (p < 0.01). CONCLUSION: Sex hormone depletion induces significant alterations in venous distensibility, presumably by inducing initial remodeling of the venous wall. Hormone dependency of distensibility differed in relaxed and contracted states of the vein, so some alterations of contractile elements of the wall may be hypothesized. Lower distensibility of the venous wall found after pharmacological ovariectomy could be part of the mechanism of predisposition for postmenopausal hypertension. This can be reversed by female sex hormone replacement.

Hormone replacement reduces elevated in vivo venous tone in hypertensive ovariectomized rats.

OBJECTIVE: The venous system may play a role in the development and progression of postmenopausal hypertension. In the present study, we investigated the effect of chronic angiotensin II-induced hypertension on the geometric, elastic, and contractile properties of the saphenous vein in sex hormone deficient and replaced female rats. METHODS: Thirty Sprague-Dawley rats were ovariectomized (n = 10), ovariectomized and angiotensin-infused (n = 10), or ovariectomized plus angiotensin-infused and hormone replaced with estradiol and medroxyprogesterone (n= 10). After 4 weeks, the saphenous veins were removed and cylindrical segments of the vessels were placed into a microangiograph and cannulated at both ends. Intraluminal pressure versus outer diameter curves were registered in Krebs-Ringer solution, in maximal norepinephrine contraction, and in full papaverine relaxation. RESULTS: In vivo venous tone of the saphenous vein in ovariectomized plus angiotensin-infused animals was significantly higher than in ovariectomized animals without angiotensin treatment (27.2 +/- 3.7% versus 5.3 +/- 2.1%, respectively; P <.05). Hormone replacement restored venous tone (9.6 +/- 3.4%; P <.01). In vitro pressure-induced myogenic tone was markedly reduced by chronic angiotensin infusion, which was partially reversed by hormone replacement. Passive incremental distensibility was lowered after angiotensin infusion independently of the sex hormone state. CONCLUSION: Hormone replacement improved venous contractility (rapid adaptation response), which was seen as decreased in vivo venous tone, but venous distensibility (chronic adaptation) was not improved by hormone replacement in our short-term study. We demonstrate beneficial short-term effects of hormone replacement on the venous system in our model of postmenopausal hypertension. Further studies might be warranted to see whether long-term benefits can be achieved.

Estrogen improves impaired musculocutaneous vascular adrenergic reactivity in pharmacologically ovariectomized rats: a potential peripheral mechanism for hot flashes?

Hot flashes are among the most common complaints of perimenopausal women. Despite the high prevalence of the phenomenon, the background to the development of hot flashes is still not completely understood, through a hypothesized central mechanism, involving norepinephrine and luteinizing hormone-releasing hormone (LH-RH) secretion is widely accepted. We studied the influence of sex steroid deficiency and hormone replacement therapy on the biomechanical properties of musculocutaneous arterioles, to see whether a peripheral mechanism also exists in the development of hot flashes. Fifty adult, nulliparous, non-pregnant female Sprague-Dawley rats received pharmacological ovariectomy, and estradiol, medroxyprogesterone, or both hormones. After 12 weeks the saphenous artery was isolated by microdissection. Norepinephrine-induced tone (active tangential strain) was measured as a function of intraluminal pressure in an organ bath. The norepinephrine-induced arterial tone was significantly different between the control group and the ovariectomized animals in the range of 80-150 mmHg intraluminal pressure (p < 0.05). Also, significant differences were found between the ovariectomized group and the animals receiving estradiol monotherapy (p < 0.01 between 80 and 170 mmHg, and p < 0.05 between 180 and 200 mmHg intraluminal pressure). Neither medroxyprogesterone monotherapy nor combined hormone replacement therapy induced significant changes in the norepinephrine-induced vascular tone. The absence of sex steroids leads to decreased reactivity to norepinephrine in small musculocutaneous arteries, while chronic estradiol replacement therapy restores the impaired responsiveness of the vessels. Our data raise the possibility that in addition to the central mechanism, a previously unknown peripheral background mechanism for perimenopausal hot flashes may exist.

Influence of long-term head-down body position on innervation density in extremity blood vessels.

The aim of the present study was to quantitate and compare the density of nerve terminals (NTD), as well as of their synaptic vesicle population (SyVD) in saphenous and brachial vein and artery, obtained from rats maintained in the horizontal or head-down tilted (HDT) position for two weeks. The same technique was applied as that for the head-up tilt study.