KUNITATE Takato Miyazaki Med. College, Dept. Physiol., Assistant, 医学部, 助手 (20234461)
HANAMORI Takamitsu Miyazaki Med. College, Dept. Physiol., Associate Professor, 医学部, 助教授 (20041858)
NISHIMORI Toshikazu Miyazaki Med. College, Dept. Biology., Professor, 医学部, 教授 (20112211)
KATO Kazuo Miyazaki Med. College, Dept. Physiol., Assistant (80284834)
ISHIZUKA Yuta Miyazaki Med. College, Dept. Psychiatry, Lecturer (20264377)
|Budget Amount *help
¥12,500,000 (Direct Cost: ¥12,500,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥7,100,000 (Direct Cost: ¥7,100,000)
Changes in adaptive responses following central salt loading have been examined with electrophysiological, neurochemical, and immunohistochemical methods. The results obtained are as follows :
(1)The effects of infusion of hypertonic saline (HS) into the lateral cerebroventricle (icv) of conscious freely-moving rats on arterial blood pressure (ABP), heart rate (HR), and renal sympathetic nerve activity (RSNA) were examined. ABP and RSNA increased and decreased, respectively, in a concentration-dependent manner, while HR did not change.
Endogenous vasopressin might be involved in salt loading-induced inhibition in the RSNA via a V_1, receptor.
(2) Next, the effects of central HS on ABP and HR in conscious rats transgenic for the metallothionin-vasopressin fusion gene (Tg), which had been provided by Dr. Yutaka Oiso (Dept. Internal Medicine, Nagoya University, School of Medicine), were examined, (a) Sprague-Dawley (SD) rats were used as the control animal. No significant differences in basa
l ABP and HR were found between SD and Tg rats. The pressor response to central HS was significantly larger in Tg than in SD rats. (b) The property of neurons in the brain, which responds to icv administration of HS was examined using Fos-like immunoreactivity (FLI) as a marker of neuronal activity in conscious Tg and SD rats. FLI expression significantly increased in the median preoptic nucleus (MnPO), the organum vasculosum laminae terminalis (OVLT), the paraventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus, and the area postrema (AP), but not in the subfornical organ (SFO), to 0.3 M HS administration. It is noteworthy that FLI expression was significantly lower in Tg rats in the PVN, SON, AP, and SFO in response to 0.15 M NaCl solution than in SD rats, (c) Vasopressin V, receptor antagonist (OPC-21268, Otsuka, Japan, 250 mg/kg, icv) did not affect basal ABP and HR but elicited a tendency to increase basal FLI expression in the PVN and SON, close to that in SD rats.
(3) To elucidate the neurochemical mechanisms responsible for the cardiovascular responses induced by central HS, the PVN region was directly perfused with HS by using an in vivo microdialysis technique. We then measured the extracellular concentration of noradrenaline (NE), nitric oxide metabolites (NOx1), and glutamate in the PVN region in conscious rats along with ABP and HR, AMP, HR, NE, NOx1, and glutamate increased by the perfusion of HS. Dizocilpine, a noncompetitive antagonist of the N-metyl-D-aspartate (NMDA) receptor, attenuated the increase of ABP and HR, although 6-cyano-7-nitroquinoxaline-2, 3-dione, an antagonist of the non-NMDA receptor, did not affect ABP or HR. Our results show that local perfusion of the hypothalamic PVN region with HS elicits a local release of various biological active substances ; among them, glutamate acts via the NMDA-type glutamate receptor to produce cardiovascular responses. Less