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Biomedical subjects

K Ohkubo

Publications and source records attributed to K Ohkubo.

At least 145 records · Page 8Linked to original sources
PubMed1984

[Pressor and depressor responses to intracerebroventricularly administered prostaglandins and arachidonic acid in anaesthetized rabbits].

The effects of intracerebroventricularly (i.c.v.) administered prostaglandins (PG) E2, F2a, I2 and their precursor, arachidonic acid (AA), on systemic blood pressure were investigated in anaesthetized rabbits. PGE2 (0.03-1 microgram/0.1 ml/rabbit) elevated blood pressure in a dose-related manner. PGF2a exerted no significant changes on blood pressure. PGI2 (0.3-10 micrograms/0.1 ml/rabbit) lowered blood pressure in a dose-related manner. AA (0.1-10 microgram/0.1 ml/rabbit) dose-independently elevated blood pressure. I.c.v. pretreatment with indomethacin, an inhibitor of cyclooxygenase, abolished the hypertensive effect of AA, but did not influence the hypertensive and hypotensive effect caused by PGE2 and PGI2, respectively. These results suggest that the hypertensive effect of AA may be composed of various actions of the above-mentioned PG and the related substances synthetized from AA in the brain tissues.

Animals↗
PubMed1982

Inhibitory mechanism of dipyridamole on platelet aggregation ex vivo.

The effects of dipyridamole on platelet aggregation ex vivo and in vitro and on platelet cyclic AMP phosphodiesterase (PDE) were studied, and the mechanism of the ex vivo effects was assessed. Both the ADP- and collagen-induced aggregations ex vivo were inhibited dose-responsively by oral administration of dipyridamole. Maximum dipyridamole levels in the plasma were reached at 30 min after the administration. The inhibitory effects of dipyridamole on platelet aggregation ex vivo reached a maximum at between 1 and 2 hrs. On the other hand, the ADP-induced aggregation in vitro and cyclic AMP PDE activity were not inhibited until after 10 min of incubation at a low concentration of dipyridamole. This mode of inhibition of platelet aggregation in vitro and of cyclic AMP PDE activity agreed with the mode of inhibition in the case of platelet aggregation ex vivo. It is suggested therefore that the ex vivo effects, observed with only a low dipyridamole concentration in the plasma, may be due primarily to inhibition by dipyridamole of the cyclic AMP PDE in platelets.

Adenosine Diphosphate↗
PubMed1982

[Central hypotensive effects of guanfacine in anaesthetised rabbits (author's transl)].

The effects of intracerebroventricular (i.c.v.) injection of guanfacine, a new antihypertensive agent, on blood pressure and heart rate were investigated and compared with those of clonidine in anaesthetized rabbits. The i.c.v. injection of guanfacine or clonidine induced a decrease in blood pressure and heart rate in doses which were ineffective by an intravenous route. The depressive effect of guanfacine was less than that of clonidine, but the duration of this action was obviously longer than that of clonidine. A fall in heart rate caused by guanfacine was always less conspicuous than that by clonidine in equipotent hypertensive doses. Decrease in blood pressure and heart rate caused by the two drugs were inhibited by i.c.v. pretreatment with phentolamine and 6-hydroxydopamine, respectively. These findings suggest that presynaptic and/or postsynaptic alpha-adrenoceptors in the brain may play an important role in the hypotension and bradycardia produced by guanfacine as well as clonidine. Furthermore, the uptake mechanism at the presynaptic sites of central noradrenergic neurons may be involved in the mode of hypotensive and bradycardic actions of these two drugs since these effects were abolished by pretreatment with desipramine, an inhibitor of noradrenaline uptake into the presynaptic nerve terminals.

Animals↗
PubMed1980

Thrombin inhibitors. 1. Ester derivatives of N alpha-(arylsulfonyl)-L-arginine.

A series of N alpha-(arylsulfonyl)-L-arginine esters was prepared and tested as inhibitors of the clotting activity of thrombin. N alpha-Dansyl-L-arginine methyl ester was the most inhibitory of the N alpha-(arylsulfonyl)-L-arginine methyl esters. The most potent inhibitors were the n-propyl and n-butyl esters of N alpha-dansyl-L-arginine with an I50 of 2 X 10(-6) M. Esters of unsaturated straight-chain alcohols with a chain length of four carbons were also as inhibitory as the n-butyl ester. The inhibitors were hydrolyzed by thrombin and trypsin more slowly than N alpha-tosyl-L-arginine methyl ester.

Animals↗
PubMed1980

Thrombin inhibitors. 2. Amide derivatives of N alpha-substituted L-arginine.

A series of N alpha-(arylsulfonyl)-L-arginine amide derivatives with substituted or unsubstituted naphthalene and heterocyclic compounds as the N alpha-substituent was prepared and tested as inhibitors of the clotting activity of thrombin. N-n-Butyl and N-n-butyl-N-methyl derivatives of N alpha-dansyl-L-arginine amide were the most inhibitory of N-alkyl and N,N-dialkyl derivatives of N alpha-dansyl-L-arginine amide. Their inhibitory effect was as potent as that of N alpha-dansyl-L-arginine-n-butyl ester with an I50 of 2 X 10(-6) M. N alpha-Substituted naphtalenesulfonyl-L-arginine amide derivatives of 4-methyl- and 4-ethylpiperidine also showed a potent inhibition with an I50 of 10(-7) to 10(-6) M. The most potent inhibitior in this study was 1-[N alpha-(4,6-dimethoxynaphthalene-2-sulfonyl)-arginyl]-4-methylpiperidine, with an I50 of 7.5 X 10(-8) M. Arginine amide derivatives of 4-methyl- or 4-ethylpiperidine with tetralin or an oxygen-containing heterocyclic compound as a N alpha-substituent showed an inhibition with an I50 less than 10(-5) M. N-Monosubstituted derivatives of N alpha-dansyl-L-arginine amide were not hydrolyzed at all by thrombin and were hydrolyzed very slowly by trypsin, and N,N-disubstituted derivatives were not hydrolyzed at all by both enzymes.

Amides↗
PubMed1980

Thrombin inhibitors. 3. Carboxyl-containing amide derivatives of N alpha-substituted L-arginine.

A series of N alpha-(arylsulfonyl)-L-arginine amide derivatives having carboxamide N-substituents with a carboxyl group was prepared and tested as inhibitors of the clotting activity of thrombin. The most inhibitory compounds were obtained when a carboxyl group was introduced into the carbon next to the amide nitrogen of N alpha-(arylsulfonyl)-L-arginine amide derivatives, e.g., N alpha-(arylsulfonyl)-L-arginyl-N-butyl-, N-(methoxyethyl)- or N-(tetrahydrofurfuryl)glycine and 4-alkyl-1-[N alpha-(arylsulfonyl)-L-arginyl]-2-piperidinecarboxylic acid, with an I50 of 1-3 X 10(-7) M.

Animals↗
PubMed1979

Early changes in the arterial endothelium under various pathological conditions: an electron histochemical study with visualization of altered permeability using electron microscopic tracers.

The authors have studied the endothelial changes in the aorta and the arteries of heart, kidney and other organs in cholesterol fed rabbits and endotoxin administrated rats through electron histochemical and vascular clearance methods. The vascular changes are variable presumably due to the functional and morphological difference of vessels. The administration of cholesterol and endotoxin may result in increased vascular permeability which is directly related to the qualitative increase and decrease of hydrolytic enzymes in the vascular wall. The permeability of high molecular substances was enhanced with the widening of the intercellular space in contraction of endothelium and the changing of molecular structure of plasma membrane accompanied with plasma lipid, platelets and hemodynamic stress. This fact was confirmed by use of horseradish peroxidase and dextran fesin as tracers of different molecular sizes. The authors emphasize that direct injury and subsequent abnormal contraction of the endothelial cell may initiate increased permeability of plasma protein and lipid in the medial layer and eventually may develop and enhance arteriosclerosis.

Acid Phosphatase↗