Nobuhiro Fujiki

Detection of hypothalamic activation by manganese ion contrasted T1-weighted magnetic resonance imaging in rats

To examine the usefulness of Mn(2+) contrasted magnetic resonance imaging (MRI) in hypothalamic imaging, images obtained using T(1)-weighted MRI were compared with Fos expression, which is known to increase after activation of voltage-dependent Ca(2+) channels. Intravenous infusion of MnCl(2) elicited a rapid increase in the T(1)-weighted MRI signal intensity in the vessels and ventricles, but not in the brain parenchyma, suggesting that Mn(2+) did not diffuse freely across the blood-brain barrier. When the blood-brain barrier was broken by right intracarotid arterial injection of 25% D-mannitol, an increased signal intensity was seen in the right brain. Intracarotid arterial injection of hypertonic NaCl elicited rapid and striking increases in signal intensity in the paraventricular hypothalamic nucleus, supraoptic nucleus, and preoptic area, which are thought to be involved in central osmotic regulation. These observations were consistent with the Fos expression results. These results indicate that Mn(2+) contrasted MRI is a useful technique for investigating the autonomic center in the hypothalamus.

Sequence of forebrain activation induced by intraventricular injection of hypertonic NaCl detected by Mn2+ contrasted T1-weighted MRI

In order to define the sequence of forebrain activation involved in osmoregulation, central activation in response to intracerebroventricular injection of NaCl solution (10 microl of 0.15, 0.5, or 1.5 M) was detected using manganese-contrasted magnetic resonance imaging (MRI) in anesthetized rats. Changes in renal sympathetic nerve activity (RNA) were also measured, and the time courses of forebrain activation and RNA changes compared. NaCl injection resulted in rapid activation of the subfornical organ (SFO), organum vasculosum lamina terminalis (OVLT), and periventricular regions and the lateral hypothalamic area (LHA), then of the paraventricular hypothalamic nucleus (PVN) and supraoptic nucleus (SON). The delay in activation in the PVN and SON showed a wide variation from 0 to 5.78 min, and the average delay in the PVN (2.88+/-0.34 min) and SON (2.90+/-0.39 min) was significantly greater than that in the SFO (0.40+/-0.10 min) and OVLT (0.74+/-0.13 min). NaCl (1.5 M) injection elicited a rapid, large increase in RNA, which consisted of two components, an early rapid increase at 99 s after injection (160+/-27%) and a slower increase at 9 min after injection (209+/-34%). These results suggest that the PVN and SON are activated not only by the afferent input from the SFO and OVLT but also by diffusion of the hypertonic stimulus to these regions and probably by their intrinsic osmosensitivity. The PVN might be responsible for the second slower component of the RNA response, but cannot be responsible for the first component.

Role of the vestibular system in sudden shutdown of renal sympathetic nerve activity during microgravity in rats

The purpose of this study was to examine the effect of microgravity (muG) on renal sympathetic nerve activity (RNA) in rats. Additionally, we estimated the participation of the vestibular system in the response of RNA to muG. Eight normal Sprague-Dawley (SD) rats and five chemically and bilaterally labyrinthectomied SD rats were used to measure RNA during free-drop examination (4.5-s duration of muG); arterial pressure (AP) and aortic flow velocity (AFV) were additionally monitored. Although AFV showed no particular change, AP tended to decrease during muG in the later phase. Prior to this AP fall-off, RNA was immediately and markedly attenuated by muG. This attenuation was transient and RNA returned to 1G level within the mu;muG condition. Interestingly, this phenomenon remained even in labyrinthectomied rats. In conclusion, cephalad shift of the body fluid by loading of muG may cause cardiopulmonary low-pressure receptor activation and consequent RNA attenuation, but the participation of the vestibulosympathetic reflex in this phenomenon is not obvious.

Acute response of aortic nerve activity to free drop-induced microgravity in anesthetized rats.

To test the hypothesis that arterial baroreflex was stimulated during microgravity (microG), arterial pressure (AP), intrathoracic pressure (ITP), and aortic nerve activity (ANA) were measured in anesthetized rats during 4.5 s of microG produced by free drop. A smooth and immediate reduction in G occurred during free drop, microG being achieved 100 ms after the start of the drop. Acute microG elicited an immediate and striking, but transient, increase in ANA, with no significant change in the AP, but a significant decrease in the end-expiratory ITP. The calculated transmural pressure of the aorta increased by 6.9 mmHg 2 s after the start of the drop. The increase in ANA lasted 2 s, then ANA returned to the control level, despite the calculated end-expiratory transmural pressure still being high. These results suggest that microG conditions stimulate the aortic baroreceptor by increasing transmural pressure by reducing the ITP. However, this effect is only transient, probably due to the high-pass property of the baroreceptors.

Response of renal sympathetic nerve activity to parabolic flight-induced gravitational change in conscious rats

The renal sympathetic nerve activity (RNA) response to gravitational changes induced by parabolic flight was examined in chronically instrumented conscious rats. Two types of RNA responses were found. In six out of 12 rats, the RNA did not respond during the 2 G period, but immediately fell to background levels on entry into microgravity (microG), then recovered to the 1 G control level during continued microG (shutdown obvious group). In the other six rats, the RNA increased to 158+/-13% at the end of the 2 G period, increased further to 195+/-22% on entry into microG, then gradually recovered to that seen at 1 G (shutdown obscure group). The mean arterial pressure in the shutdown obvious group was significantly higher and the heart rate tended to be higher than in the shutdown obscure group, suggesting that the baseline sympathetic tone in the shutdown obvious group was higher than in the shutdown obscure group. These results suggest that the RNA response to parabolic flight might be affected by the baseline sympathetic tone.

Acute responses of renal nerve activity to microgravity induced by free drop in anesthetized rats

To examine acute cardiovascular and autonomic responses to microgravity (microG), arterial pressure (AP), aortic flow velocity (AFV), central venous pressure (CVP), and renal nerve activity (RNA) were measured in anesthetized rats during 4.5 s of microG produced by free drop. A smooth and immediate reduction in gravity occurred during free drop, microG being achieved 100 ms after the start of the drop. Acute microG elicited an immediate and striking, but transient, decrease in RNA with no significant change in AP and AFV, but a significant decrease in CVP. The decrease in RNA lasted 2 s, then RNA recovered to the control level despite the G value remaining at < 0.001 for 4.5 s. The RNA decrease was attenuated or completely abolished by sinoaortic denervation, vagotomy, or sinoaortic denervation plus vagotomy. These results suggest that acute microG conditions stimulate sinoaortic and cardiopulmonary mechanoreceptors and suppress RNA.

Increased oxytocin-monomeric red fluorescent protein 1 fluorescent intensity with urocortin-like immunoreactivity in the hypothalamo-neurohypophysial system of aged transgenic rats

To visualize oxytocin in the hypothalamo-neurohypophysial system, we generated a transgenic rat that expresses the oxytocin-monomeric red fluorescent protein 1 (mRFP1) fusion gene. In the present study, we examined the age-related changes of oxytocin-mRFP1 fluorescent intensity in the posterior pituitary (PP), the supraoptic nucleus (SON) and the paraventricular nucleus (PVN) of transgenic rats. The mRFP1 fluorescent intensities were significantly increased in the PP, the SON and the PVN of 12-, 18- and 24-month-old transgenic rats in comparison with 3-month-old transgenic rats. Immunohistochemical staining for urocortin, which belongs to the family of corticotropin-releasing factor family, revealed that the numbers of urocortin-like immunoreactive (LI) cells in the SON and the PVN were significantly increased in 12-, 18- and 24-month-old transgenic rats in comparison with 3-month-old transgenic rats. Almost all of urocortin-LI cells co-exist mRFP1-expressing cells in the SON and the PVN of aged transgenic rats. These results suggest that oxytocin content of the hypothalamo-neurohypophysial system may be modulated by age-related regulation. The physiological role of the co-existence of oxytocin and urocortin in the SON and PVN of aged rats remains unclear.

Sulfite suppresses transducer function of the carotid sinus baroreceptor

Abstract The purpose of this study was to examine the effect of sodium metabisulfite (MBS) solution on the transducer function of the carotid sinus baroreceptor. In anesthetized dogs with vagotomy, we vascularly isolated the carotid bifurcation to load a pressure on the carotid sinus baroreceptor. As the pressure load, we used a slow ramp increase (0.7 mmHg/s) in intracarotid sinus pressure (ICSP). The response of carotid sinus nerve activity (CSNA) to the slow ramp increase in ICSP was suppressed when the isolated carotid sinus was filled with the MBS solution of 10-2M. This suppressive effect of MBS solution on the response of CSNA was reversible. The MBS solution had no effect on the pressure-volume relationship of the arterial wall of the isolated carotid sinus and on the impulse conduction of carotid sinus nerve. This suppressive effect of the MBS solution of 10-2 M was weakened by introducing oxygen gas into the solution to lose the total sulfite anions in the solution. These results suggest that: (1) the MBS solution reversibly suppresses the transducer function of the carotid sinus baroreceptor; (2) the target construction of the carotid sinus region that was affected by the MBS solution might be the carotid sinus baroreceptor nerve terminal where ICSP was transduced into carotid sinus nerve firing; and (3) the suppressive effect might be provoked by the sulfite anions in the MBS solution.