山﨑 将生

To investigate whether daily orthostatic stress during development is an important factor affecting arterial baroreceptor reflex function, we examined the effect of chronic inhibition of upright standing behaviour on the baroreceptor reflex function in rats. Upright standing behaviour was chronically inhibited during the developmental period between 3 and 8 weeks of age in Sprague-Dawley rats and heart rate (HR) and aortic nerve activity in response to increased and decreased mean arterial pressure (MAP) was measured after the treatment period. The baroreceptor cardiac gain in the rats grown without standing behaviour was significantly lower than the control rats grown in a normal commercial cage (1.0 +/- 0.1 beats min(-1) mmHg(-1) vs. 1.6 +/- 0.2 beatsmin(-1) mmHg(-1), P < 0.05). The range of HR change in the MAP-HR functional curve was also lowered by chronic inhibition of orthostatic behaviour (56.2 +/- 5.9 beats min(-1)) compared with that of the control rats (76.8 +/- 6.9 beats min(-1), P < 0.05). However the aortic afferent function remained normal after the treatment period, indicating that the attenuated baroreceptor reflex function may be due to other mechanisms involving functional alterations in the cardiovascular centres, efferents and/or peripheral organs. Body weight and adrenal weight were not affected by the inhibition of orthostatic behaviour, suggesting that the animals were not exposed to specific stress by this treatment. These results indicate that active haemodynamic changes induced by orthostatic behaviour are an important factor for setting the basal level of reflex function during development. Moreover, our experimental model may be useful for studying mechanisms of attenuated baroreceptor reflex observed after exposure to a chronic inactive condition.

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.

Aim: It has been reported that spaceflight attenuates the arterial baroreceptor reflex. As this reflex function changes dramatically during postnatal development, we hypothesized that space flight depresses the developmental changes of the reflex system. To test this hypothesis, we evaluated the baroreceptor reflex function in rats, which were exposed to a microgravity environment on a space shuttle 9-25 days after birth. Methods: Baroreceptor reflex sensitivity and the afferent sensitivity were evaluated by measuring heart rate (HR) and aortic nerve activity (ANA) changes in response to an increase in mean arterial pressure (MBP) derived by phenylephrine injection (20-50 μg kg-1) under urethane-anaesthesia. Results: Baroreceptor reflex sensitivity (% change of HR/% change of MBP) was lower in the flight group (FLT: -0.19 ± 0.04, n = 4) than either the asynchronous ground control group (AGC: -0.47 ± 0.06, n = 6, P &lt 0.01) or the vivarium group (VIV: -0.41 ± 0.07, n = 6, P &lt 0.05). This was similar to the differences of the afferent sensitivity (% change of ANA/% change of MBP) between FLT (2.07 ± 0.30) and the control groups (AGC: 2.71 ± 0.22, n.s. VIV: 3.00 ± 0.32, P &lt 0.05). At the end of 30 days of recovery under normal gravity conditions, however, there were no significant group differences in these parameters. Conclusion: These results suggest that the space environment attenuates the postnatal development of the arterial baroreceptor reflex function in rats, which may be partially because of a depression of the postnatal development of the baroreceptor afferents. These functional alterations, however, recover to their normal level on re-exposure to the Earth's gravity. © 2005 Scandinavian Physiological Society.

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.