山﨑 将生

We investigated effect of microgravity environment during spaceflight on postnatal development of the rheological properties of the aorta in rats. The neonate rats were randomly divided at 7 days of age into the spaceflight, asynchronous ground control, and vivarium control groups (8 pups for one dam). The spaceflight group rats at 9 days of age were exposed to microgravity environment for 16 days. A longitudinal wall strip of the proximal descending thoracic aorta was subjected to stress-strain and stress-relaxation tests. Wall tensile force was significantly smaller in the spaceflight group than in the two control groups, whereas there were no significant differences in wall stress or incremental elastic modulus at each strain among the three groups. Wall thickness and number of smooth muscle fibers were significantly smaller in the spaceflight group than in the two control groups, but there were no significant differences in amounts of either the elastin or collagen fibers among the three groups. The decreased thickness was mainly caused by the decreased number of smooth muscle cells. Plastic deformation was observed only in the spaceflight group in the stress-strain test. A microgravity environment during spaceflight could affect postnatal development of the morphological and rheological properties of the aorta.

Although rats often show an upright standing behavior the cardiovascular response during the behavior has not yet been fully clarified. In this study we quantified the activity of upright standing behavior in rats using infrared beam detectors and measured cardiovascular variables during the behavior. Rats demonstrated a high level of upright standing activity as they showed the upright posture more than 500 times per day at 10 weeks of age. The average upright standing duration time was less than 10s. Arterial pressure slightly decreased while heart rate increased in response to the behavior and these responses were not affected by sino-aortic denervation. Our results indicate that other mechanisms such as the vestibulo-cardiovascular reflex may completely compensate the lack of the baroreceptor reflex to maintain cardiovascular homeostasis in response to acute positional changes in rats. Moreover rats demonstrate complex integrative mechanisms maintaining cardiovascular homeostasis against the upright standing behavior which frequently occurs in rats. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

To investigate whether the rate of change in blood pressure affects the sensitivity of the aortic baroreceptor afferent response, the change in aortic nerve activity (ANA) to two different rates of ramp increase in mean blood pressure (MBP), elicited by phenylephrine administration, was determined in the rat under urethane (1.5 g kg(-1)) anesthesia. The sensitivity of the increase in ANA following a rapid (average ramp rate, 9.14 +/- 0.60 mmHg s(-1), n = 11) or gradual (1.78 +/- 0.24 mmHg s(-1), n = 11) increase in MBP was 2.03 +/- 0.14% and 1.81 +/- 0.20% of baseline mmHg(-1), respectively. These values were not significantly different from each other (P = 0.16). Furthermore, we found no correlation between the rate of ramp increase in MBP and the sensitivity of the increase in ANA (r = 0.24, P = 0.29, n = 22). These results suggest that, at least within the normal physiological range of MBP, the rate of the ramp change in blood pressure does not affect aortic baroreceptor afferent sensitivity in the anesthetized rat. (c) 2008 Elsevier Ireland Ltd. All rights reserved

To investigate postnatal developmental changes in functional characteristics of the afferent pathway of the aortic baroreceptor reflex, the responses of aortic nerve activity (ANA) to blood pressure (BP) changes elicited by phenylephrine and sodium nitroprusside administration were tested in 3-, 8- and 20-week-old male rats under chloralose (60 mg kg(-1) I.P.) and urethane (600 mg kg(-1) I.P.) anaesthesia. The function curve of ANA in response to BP changes showed a sigmoid shape that shifted to the right from 3 to 8 weeks of age. The maximal activity and maximal gain of the aortic nerve, which were calculated by a logistic function analysis, were significantly higher in 20-week-old rats (maximal activity, 532 +/- 47% of baseline; maximal gain, 7.9 +/- 0.8% of baseline mmHg(-1); n = 9) than in 3-week-old rats (maximal ANA, 268 +/- 25% of baseline, P < 0.001; maximal gain, 4.9 +/- 0.5% of baseline mmHg(-1), P < 0.01, n = 9) and 8-week-old rats (maximal ANA, 309 +/- 18% of baseline, P < 0.001; maximal gain, 4.9 +/- 0.3% of baseline mmHg(-1), P < 0.01, n = 11). These results suggest that the operating point of aortic baroreceptor afferents is reset to the higher pressure level during development from 3 to 8 weeks of age and, thereafter, the afferent gain increases from 8 to 20 weeks of age. This functional change may be an important factor to prevent an excess increase of BP, which would result in pathophysiological problems.

The effects of microgravity on the histological characteristics of the aortic depressor nerve, which is the afferent of the aortic baroreflex arc, were determined in 10 female adult rats. The rats were assigned for nursing neonates in the Space Shuttle Columbia or in the animal facility on the ground (NASA Neurolab, STS-90), and were housed for 16 days under microgravity in space (μg, n=5) or under one force of gravity on Earth (one-g, n=5). In the Schwann cell unit in which the axons of unmyelinated fibers are surrounded by one Schwann cell, the average number of axons per unit in the μg group was 2.1 ± 1.6 (mean ± SD, n=312) and significantly less than that in the one-g group (3.0 ± 2.9, n=397, p<0.05). The proportion of unmyelinated fibers in the aortic depressor nerve in the μg group was 64.5 ± 4.4% and significantly less than that in the one-g group(74.0 ± 7.3%, p<0.05). These results show that there is a decrease in the number of high-threshold unmyelinated fibers in the aortic depressor nerve in adult rats flown on the Shuttle Orbiter, suggesting that the aortic baroreflex is depressed under microgravity during space flight.

Hydrostatic pressure gradients due to the gravitational force in blood vessels disappear under conditions of microgravity during spaceflight, and the ability of the baroreceptor reflex to control arterial pressure and blood distribution may be altered. We hypothesized, on the basis of the results obtained in our previous experiments using the head-down tilt method in rats and rabbits, that the range of increase in arterial pressure caused by animal behavior narrows under conditions of microgravity, affecting the development of high-threshold unmyelinated fibers in the rat aortic nerve which sends signals from baroreceptors located in the aortic wall to the reflex center. We verified this hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched neonatal rats with the dams remained on the ground as controls. After breeding was carried out in the three experimental groups (FLT, spaceflight; AGC, asynchronous ground control; VIV, vivarium ground control), specimens of the 25-day-old rats were excised and five left aortic nerves in each group were examined by electron microscopy. The number of aortic unmyelinated fibers was significantly less in the FLT group than in each ground control (mean+/-S.D.; 139+/-37 in the FLT, 207 36 in the AGC, 283+/-121 in the VIV; P&lt;0.05), which may be related to the weakness of the baroreceptor reflex under conditions of microgravity in space. This result may contribute to understanding of the several cardiovascular issues which occur under microgravity and after reexposure to gravity in human. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.

Abdominal aortic pressure (AAP), heart rate (HR), and aortic nerve activity (ANA) during parabolic flight were measured by using a telemetry system to clarify the acute effect of microgravity (muG) on hemodynamics in rats. While the animals were conscious, AAP increased up to 119 +/- 3 mmHg on exposure to muG compared with the value at 1 G (95 +/- 3 mmHg; P &lt; 0.001), whereas AAP decreased immediately on exposure to &mu;G under urethane anesthesia (&mu;G: 72 &PLUSMN; 9 mmHg vs. 1 G: 78 &PLUSMN; 8 mmHg; P &lt; 0.05). HR also increased during muG in conscious animals (muG: 349 +/- 12 beats/min vs. 1 G: 324+9 beats/min; P &lt; 0.01), although no change was observed under anesthesia. ANA, which was measured under anesthesia, decreased in response to acute &mu;G exposure (&mu;G: 33 &PLUSMN; 7 counts/s vs. 1 G: 49 &PLUSMN; 5 counts/s; P &lt; 0.01). These results suggest that muG essentially induces a decrease of arterial pressure; however, emotional stress and body movements affect the responses of arterial pressure and HR during exposure to acute muG.

To clarify the effects of the head-down tilt (HDT) posture on the postnatal development of the aortic baroreflex, we raised rabbits from 3-4 weeks of age for 34-36 d in this posture, which simulates the headward shift of body fluid in space, and examined the structural and functional characteristics of the aortic nerves and baroreflex responses. The rabbits were divided into 3 different groups: 20degrees HDT, environmental control (EC), and vivarium control (VIV). Left aortic nerve activity (ANA) at basal arterial pressure was defined as 100%, and the maximum ANA at maximal increase in arterial pressure was 265+/-103% (mean+/-SD, n=5) in the HDT, 482+/-170% (n=4) in the EC, and 677+/-491% (n=4) in the VIV groups. The minimum ANA at maximal decrease in arterial pressure was 67.3+/-13.8% in the HDT, 40.1+/-10.2% in the EC, and 38.6+/-13.8% in the VIV groups. The maximal change of ANA in response to maximal change in arterial pressure in the HDT group was significantly less than that of either the EC or VIV group (p&lt;0.05). The average baroreflex gain in the HDT group was significantly less than in the VIV group (p&lt;0.05). The number of unmyelinated fibers in the left aortic nerve in the HDT group was significantly less than that of each control group ( p&lt;0.05). Thus the development of the aortic baroreflex system is apparently depressed by the HDT posture, suggesting that similar consequences will be observed in mammals that develop in space.

Postnatal changes in the rheological properties of the aortic wall were investigated in relation to morphological development of the wall in Sprague-Dawley (SD) rats at 3, 8 and 20 weeks old. The mechanical tensile characteristics of the longitudinal wall strip excised from the proximal thoracic aorta were assessed with stress-strain and stress-relaxation tests. Wall tension in the low and medium strain ranges was significantly lower in 3-week-old rats than in 8-week-old rats and in 8-week-old rats than in 20-week-old rats. Wall stress was significantly lower in 3-week-old rats than in 8- and 20-week-old rats mainly in the medium strain range, but was significantly greater in 3-week-old rats than in 8- and 20-week-old rats in the high strain range. The value of incremental elastic modulus at 3 weeks old was significantly smaller than that at 8 and 20 weeks old at a strain of 0.25 and significantly larger than that at 8 and 20 weeks old at a strain of 0.50. The value of relaxation strength at 5 min after the stretching was significantly greater at 3 weeks old than that at 8 and 20 weeks old. The wall was viscoelastic in the low and medium strain ranges at 3 weeks though large wall stress was generated in the high strain range. Histological investigation revealed that the smooth muscle layer, fine elastin fiber connecting thick elastin fibers and wall thickness were thin at 3 weeks old in comparison with those at 8 and 20 weeks old, though there was no significant difference in number of nuclei of the smooth muscle cells among the three age groups. Changes in the tensile characteristics of the wall reflected well those of the microstructure of the wall with growth. The rheological properties and microstructure of the aortic wall were close to maturation at 8 weeks in SD rats.