Antihypertensive effects of three β-adrenergic blocking drugs, acebutolol, propranolol, and practolol were studied for 11 weeks. Spontaneously (SHR) ; one-clip, two-kidney (CLIP) ; and deoxycorticosterone and salt (DOC) hypertensive rats were used. The drugs were given orally, 100 mg/kg per day, 5 days per week before development of hypertension. Propranolol inhibited blood pressure (BP) increase significantly in SHR. Acebutolol and practolol also lowered BP in SHR. Three drugs did not affect BP in CLIP, but an apparent inhibition was seen when the results were analyzed including the cases of which BP stayed below 150 mmHg. Either of three drugs did not show antihypertensive effects in DOC. Acebutolol rather increased BP more rapidly. Practolol also increased BP slightly more rapidly. Cerebral stroke was seen in DOC. The incidences of the stroke in the groups given the solvent, acebutolol, propranolol, and practolol were 3/6, 4/7, 2/6, and 3/6, respectively. Acebutolol seemed to cause stroke earlier with the more rapid BP elevation. Acebutolol, propranolol, and practolol decreased incidence of the vascular disease in CLIP. Propranolol also decreased it in DOC. Plasma renin activity was suppressed by these drugs in SHR and CLIP. The mechanisms of antihypertensive effects of β-adrenergic blocking drugs are unknown. The present study denies those due to inhibition of cardiac function, or renin release from the kidney. A better experimental model is necessary to study this. The possibility that acebutolol and other β-blockers might accelerate BP elevation and incidence of stroke must be reexamined.

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To determine whether initial sympatho-adrenal stimulation during stress was responsible for inducing a parasympathetic stimulation, the autonomic nervous activities were estimated in rats subjected to either restraint stress or restraint and water immersion stress. The parasympathetic and sympatho-adrenal activities were estimated functionally by measuring responses of gastric motility and heart rate, and also chemically by measuring catecholamine content in urine and tissues such as the heart and adrenals. Restraint and water immersion produced a definite parasympathetic predominance in contrast to the case of restraint alone. But both kinds of stress developed an increase in the sympatho-adrenal activity, and the extent of their increase was almost the same when evaluated on the basis of urinary catecholamine content. These findings indicate that initial sympatho-adrenal stimulation is not directly associated with parasympathetic stimulation. A marked fall in body temperature during stress was assumed to participate somewhere in the induction of parasympathetic stimulation.

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Comparative metabolic fate of labelled chromium chloride and sodium chromate and interaction of these compounds in the rat liver and blood were investigated after their oral and intravenous administration. Gastrointestinal absorption of both compounds was below 1% of the oral dose, but trivalent chromium showed higher radioactivity than the hexavalent form in rats (biological half-life : CrCl₃ 91.79 days, Na₂CrO₄ 22.24 days). The higher residual activity of the trivalent chromium was also observed after intravenous administration. Both forms of chromium were excreted more in the urine via the kidney than in the intestinal tract after intravenous administration. When ⁵¹CrCl₃ and Na₂⁵¹CrO₄ were injected into rats, in the time-distribution patterns of ⁵¹Cr in the organs, a significant difference was shown between oxidation states of the two compounds, especially in subcellular fractions of the liver and blood constituents. This significant difference mainly observed in the rat blood came from the fact that trivalent chromium possessed a high binding activity for transferrin in plasma, while hexavalent chromium was permeable into red cells and bound with hemoglobin.

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The effect of gel preparation on the rate of absorption of a rectally administered insulin which was suspended in a polyacrylic acid aqueous gel base (0.1%, pH 6.5) was investigated in the alloxan diabetic rats and rabbits. The preparation was administered into the in situ rectal loop in rats or infused directly into the rectum in rabbits, and the change in the blood glucose level and plasma insulin value was taken as a measure to evaluate the rate of rectal absorption of insulin. The blood glucose lowering effect in both rats and rabbits was dose-dependent, namely, a slight effect was observed at 1 IU/kg followed by a significant effect with 3 and 5 IU/kg, and a sharp hypoglycemic effect was recorded with 10 IU/kg which lasted for 5 hr. The plasma insulin level exhibited a rapid increase at 30 minutes after the dosing of the insulin gel at 3 IU/kg, which is indicative of a facilitated rectal rate of absorption of insulin by the polyacrylic acid aqueous gel base. However, the plasma level quickly diminished in 1 hr. Contrary to our expectation, an addition of a non-ionic surfactant such as Tween 80 under pH 4-8 did not show further enhancement of the absorption. In an attempt to simulate a clinical condition in which insulin was given after a meal, the insulin gel was administered into the rectal loop in diabetic rats following the i.v. injection of glucose. A satisfactory result was obtained in which 5 IU/kg dose was able to suppress a rise in the blood glucose after the glucose loading.

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Three kinds of plasma membranes in rat islet homogenate were fractionated on sucrose gradient centrifuged at 70000g (F₁ : d²⁰=1.14-1.18, F₂ : d²⁰=1.06-1.12, F₃ : d²⁰=1.02-1.05). Every fraction indicated both enzyme activities of 5'-nucleotidase and ATPase which were typical marker enzymes in pancreatic plasma membrane, and the D-[5-³H] glucose binding with them were dose-dependently inhibited by D-glucose, but not by L-glucose, D-galactose and 3-O-methyl-D-glucose. The D-[5-³H] glucose binding with only F₂ fraction was inhibited by D-mannose and D-fructose which could stimulate insulin release (60%), phlorizin inhibited remarkably the binding with F₃ fraction (68%), however, the D-[5-³H] glucose binding with either F₁ or F₂ fraction was slightly inhibited by preincubation with alloxan (0.2 mg/ml, 37°, 10min) (F₁ : 29%, F₂ : 39%) and that with F₃ fraction was not effective (4%). It was found that the insulin release from the B granules which distributed in the pellet fraction on sucrose gradient centrifuged at 70000g, was induced by the interaction with F₂ fraction. Each maximal capacity of glucose binding site in F₁, F₂ and F₃ fractions was estimated at 3.2, 1.0 and 3.2 μmol/mg membrane protein, respectively, from those Scatchard's plots for the glucose binding. Consequently, it was estimated that the membrane which associated with insulin release was contained in F₂ fraction among three fractions from the islet homogenate.

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The relationships between the structure and inhibitory activity against the formation of acid-fastness in mycobacterial organisms were investigated in naturally occurring or synthetic coumarins and cinnamates. The presence of an OH-group at C₇ in the coumarin nucleus proved to be essential for the inhibitory activity. Likewise, the presence of a para-OH-group in cinnamates is also essential. Reduction of a conjugated α, β-double bond in both series resulted in a decrease of the ininhibitory activity. Shortening of the side chain of cinnamates resulted in total loss of the activity. The grouping 〓〓CO₂R appeared to be necessary for retaining the inhibitory activity.

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The effects of some neuroleptic butyrophenones such as haloperidol, clofluperol, trifluperidol, lenperone, moperone, and floropipamide on pituitary-adrenal activity were studied in rats following a single i.p. administration. All the drugs examined caused a marked increase in the plasma and adrenal corticosterone concentrations. The actions of haloperidol, clofluperol, and trifluperidol were shown to be most potent, while floropipamide was the weakest among them. The stimulatory effect of the drugs on adrenocortical activity was completely inhibited by either dexamethasone pretreatment or hypophysectomy and was shown not to be merely due to a consequence of a drug-induced hypothermia. These results indicate that the release of ACTH from the adenohypophysis is necessary for the drug action.

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Hepatotoxic action of CHCl₃ was examined biochemically by comparing with those of CCl₄ and other related halogenomethanes using normal and phenobarbital (PB)-pretreated animals. In the later stage (24 hr), in mice, PB pretreatment augmented CHCl₃-induced liver damage as evidenced by an enhancement of elevation of plasma transaminase activities and a parallel rise in liver triglyceride content. In the earlier stage (1 hr), in normal rats, CCl₄ (1.0 ml/kg, i.p.) decreased microsomal glucose-6-phosphatase (G-6-Pase) activity and cytochrome P-450 content, whereas no significant effect was observed with the same dose of CHCl₃. PB pretreatment produced a significant loss of both enzymes by CHCl₃, and enhanced the loss of cytochrome P-450 induced by CCl₄, while G-6-Pase activity was little affected by CCl₄ in PB-pretreated rats. Both hepatotoxins increased liver malondialdehyde (MDA) content. Some of these early changes in vivo were reproduced in the lipid peroxidation system in vitro. Diethyldithiocarbamate suppressed various toxic manifestations induced by CHCl₃ in PB-pretreated rats, but did not protect against the loss of cytochrome P-450 induced by CHCl₃ or CCl₄. These results suggest that lipid peroxidation hypothesis proposed for CCl₄ hepatotoxicity may be applied to the case of CHCl₃ though there exist some qualitatively different characteristics between these hepatotoxins, and that the mechanisms of the loss of microsomal G-6-Pase and cytochrome P-450 by either of these hepatotoxins might be different.

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Effects of papaverine, Aspaminol (an antispasmodic drug), D-600, 2, 4-dinitrophenol and Ca ions on glycogen phosphorylase activity in the KCl-depolarized taenia caecum of guinea pig were tested. External Ca ions dose-dependently activated phosphrylase, indicating that Ca ions, which entered the smooth muscle cells, played an important role in the regulation of phosphorylase activity. Aspaminol, D-600 and removal of Ca ions from bath fluid inhibited phosphorylase activity. Since these treatments relaxed the taenia caecum, the decrease of phosphorylase activity after the treatments may be mainly due to the decrease of energy consumption. Papaverine and 2, 4-dinitrophenol induced an activation of phosphrylase which might be for replenishment of energy stores decreased by them.

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