Katsuhiro Watanabe

Effect of thyrotropin-releasing hormone on cerebral blood flow in conscious rat

The effect of thyrotropin-releasing hormone (TRH) was studied on local CBF (LCBF) in normal conscious rats. LCBF was measured by the autoradiographic [14C]iodoantipyrine method 5 min after TRH (5 mg/kg, i.v.) administration. TRH significantly increased LCBF in 22 of 33 brain regions. This increase of LCBF exceeded 100% of the control values in the cerebral cortices, whereas there was no significant increase in white matter or in some gray matter structures. The increase of CBF following TRH administration was abolished by pretreatment with indomethacin (5 mg/kg, i.v.). The mechanisms underlying the increase of CBF following TRH administration are discussed in relation to prostaglandin metabolism.

Lactate in the Cerebrospinal Fluid and Pressure-Flow Relationships in Canine Cerebral Circulation

In 11 dogs, lactate and pH in the cerebrospinal fluid and in the arterial and the venous blood were measured during stepwise reductions of the arterial blood pressure by controlled bleeding. Increase in lactate and decrease in pH of the cerebrospinal fluid occurred with lowering of the mean arterial blood pressure even within the pressure ranges of 110 to 50 mm Hg, where autoregulation was fairly observed. Reductions of the blood pressure by 20 to 40 mm Hg led to a significant increase in lactate, and reductions by 60 mm Hg led to a significant decrease in pH of the cerebrospinal fluid. The relation of decrease in pH and increase in lactate was linear, suggesting that lactacidosis occurred. In the arterial and the venous blood, a marked increase in lactate and decrease in pH also were observed. Lactate concentrations of the cerebral venous blood were significantly higher than those of the arterial blood until the arterial blood pressure had been reduced below 70 mm Hg. Therefore, it was suggested that increase in lactate of the cerebrospinal fluid might be attributed solely to increase in lactate of the brain tissue, so far as the blood pressure was not lowered below 70 mm Hg at least. The possibility of participation of the cerebrospinal fluid lactacidosis in autoregulation of the cerebral blood flow was discussed.

Effects of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brainIn Vivo

The effect of HA1077, an intracellular calcium antagonist, on neurotransmitter metabolism in rat brain was investigated in vivo. After administration of HA1077, at doses of 0.1, 0.3, and 3 mg/kg, 5-hydroxyindoleacetic acid (5-HIAA) levels increased in most regions except midbrain. In the striatum, parallel increases of both serotonin (5-HT) and 5-HIAA levels were observed at 0.3 mg/kg, but only the 5-HT level increased at 0.1 mg/kg. These results suggest that HA1077 may activate the turnover or synthesis of 5-HT. After administration of HA1077 at 0.3, 1, and 3 mg/kg, the dopamine (DA) level was increased in the striatum, but 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid levels were unchanged. After HA1077 administration at 1 mg/kg, both DA and DOPAC levels increased in the hypothalamus and only DA level increased in the cerebral cortex. By contrast, DOPAC level decreased in the midbrain after HA1077 treatment at 0.1 and 0.3 mg/kg, and in the brainstem at 0.1 and 10 mg/kg. The ratio of [3H]-N-methylspiperone accumulation relative to that in the cerebellum did not change after HA1077 treatment at any of the doses employed. Thus, the effects of HA1077 on neurotransmitter metabolism are complex and vary depending on the dosage and sites of the brain. Although the dose-dependent effects of HA1077 on neurotransmitter metabolism are similar to those of calcium entry blockers, HA1077 can facilitate DA synthesis in the hypothalamus and striatum, unlike the calcium entry blockers.

ラット脳内Cyclic nucleotidesにおよぼすClonidineの影響―Clonidine単独投与時およびα遮断薬併用時の変化―

The following 4 Wistar rat groups were sacrificed by microwave irradiation after measuring blood pressure and heart rate: 1) saline control (1 ml/kg, i.v.), 2) clonidine alone (50 micrograms/kg, i.v.). 3) prazosin pretreated (0.1 mg/kg, i.v.), 4) yohimbine pretreated (1 mg/kg, i.v.). Cyclic nucleotides were analyzed in seven brain regions. Clonidine decreased blood pressure and heart rate 20 min after administration. These effects of clonidine were inhibited by yohimbine. Clonidine increased the levels of cyclic AMP in the medulla oblongata (including pons) and hypothalamus. Prazosin attenuated the cyclic AMP-increasing action of clonidine in the cerebellum. Yohimbine inhibited this action of clonidine in the cerebellum, striatum and hippocampus. Clonidine reduced cyclic GMP levels in the hypothalamus and striatum. Prazosin potentiated the cyclic GMP-reducing action of clonidine in the medulla oblongata. Yohimbine attenuated this action of clonidine in the medulla oblongata and hypothalamus. From these results, it is concluded that clonidine changes the levels of cyclic nucleotides in brain regions, especially in the part of the autonomic nervous center. In addition, it is indicated that alpha 1- or alpha 2-adrenoceptor plays a different role in the regulation of brain cyclic nucleotides, region by region.

Effects of guanfacine on the levels of cyclic nucleotides in anesthetized rat brain regions.

Effects of an antihypertensive drug, guanfacine, on brain regional cyclic AMP and cyclic GMP levels were studied in anesthetized rats. Cyclic nucleotides were analyzed in seven brain regions. Guanfacine decreased blood pressure and heart rate 20 min after administration. Yohimbine inhibited these hemodynamic effects of guanfacine. Guanfacine reduced cyclic AMP levels in the hypothalamus. The reducing effect of guanfacine on cyclic AMP was antagonized by yohimbine in the hypothalamus. Guanfacine lowered cyclic GMP in the cerebellum, medulla oblongata and hypothalamus. Yohimbine inhibited the effect of guanfacine on cyclic GMP in the cerebellum, medulla oblongata and hypothalamus. Prazosin showed no effect on guanfacine induced change of cyclic nucleotides in any brain region. From these results, it is concluded that guanfacine decreased cyclic AMP and cyclic GMP in the hypothalamus. In addition, it is suggested that alpha-2 adrenoceptors mainly modulate these changes of cyclic nucleotides.