PubMed Health⌕ Search

Biomedical subjects

S Kumakura

Publications and source records attributed to S Kumakura.

At least 55 records · Page 3Linked to original sources
PubMed1988

Cardiovascular pharmacology of RS-1893, an orally active cardiotonic agent with arterial and venous vasodilator actions.

RS-1893, 2-[2-chloro-4-(2,3,4,5-tetrahydro-3-oxo-6-pyridazinyl)]-phenoxy-N- (2-(2-morpholinoethyl)-acetamide, is a newly synthesized compound whose structure is different from that of cardiac glycosides and beta-stimulants. The in vitro cardiotonic action of RS-1893 was about 3 times more potent than that of milrinone. This action is most likely due to inhibition of phosphodiesterase-III, as has been suggested for many other cardiotonic agents. In pentobarbital anesthetized dogs, RS-1893 (1-30 micrograms/kg, i.v.) produced dose dependent increases in left ventricular dP/dtmax and cardiac output and caused decreases in blood pressure and total peripheral resistance with a relatively small increase in heart rate. Central venous pressure decreased markedly, suggesting venous vasodilation. The in vivo cardiotonic action of RS-1893 was 3 times more potent than that of milrinone and was not affected in the presence of a large dose of propranolol. Oral administration of RS-1893 (0.03 and 0.1 mg/kg) also produced a dose-related increase in cardiac contractility in conscious beagles. The increase in LVdP/dtmax reached a maximum in 1-3 hr after administration and lasted for more than 8 hr. Thus, RS-1893 appeared to be an orally active cardiotonic agent with vasodilator properties, probably acting on both arterioles and veins.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1987

Role of bradykinin generating and degrading systems in the vascular permeability response induced with kaolin in rats.

We investigated how bradykinin mediates inflammatory reactions in rats, via measurements of bradykinin by enzyme immunoassay method in inflammatory tissue fluids. Vascular permeability was increased markedly during the first 10 min and then declined quickly after the infusion of a kaolin suspension (10 mg/ml) in 0.8% carboxymethl-cellulose solution into an air pouch formed on the back of rats. Bradykinin in the exudate reached a maximum 5 min after the challenge and then decreased quickly. Local treatment with DL-2-mercaptomethyl-3-guanidinoethylthiopropanoic acid, an inhibitor of kininase I, and captopril, an inhibitor of kininase II in the first 10-min period, each enhanced the vascular permeability increase accompanied by the elevation of the bradykinin level, whereas soybean trypsin inhibitor, a plasma kallikrein inhibitor, lowered both vascular permeability and bradykinin. When applied in the period of 3.5 to 4 hr after the challenge, only the kininase II inhibitor was effective in elevating both vascular permeability and the bradykinin level, whereas soybean trypsin inhibitor was ineffective on vascular permeability. A bradykinin-degrading activity appeared in the exudate as early as 10 min after the challenge. These results suggest that bradykinin plays an essential role for the sudden rise of the vascular permeability observed immediately after the infusion of kaolin suspension. In the later stage (3.5-4 hr), bradykinin level remained below the assay limit of 0.07 ng/ml in spite of its active generation, presumably because of its rapid degradation by the kininases, although it still played a definite role in the vascular permeability increase.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

A case of partial hypopituitarism with empty sella following normal course of pregnancy and delivery.

A 28 year-old woman was admitted to Jichi Medical School Hospital because of amenorrhea, cold intolerance, easy fatigability and body weight loss. She was pregnant at the age of 26 years. She delivered a 3230 g healthy girl at full term without any complications. However, she did not have any lactation or recurrence of menstruation after the delivery. Serum cortisol was 0.7 micrograms/dl, and plasma adrenocorticotropic hormone (ACTH) was less than 10 pg/ml. Both hormones failed to increase in response to insulin-induced hypoglycemia or exogenous arginine vasopressin. However, serum cortisol and urinary excretion of 17-hydroxycorticosteroids (17-OHCS) were significantly increased by the repeated administration of ACTH. Serum prolactin was 2.2 ng/ml and the level did not rise after the administration of thyrotropin releasing hormone (TRH). Responses of release of adenohypophysial hormones including gonadotropins, growth hormone and thyroid stimulating hormone (TSH) were normal. Serological studies showed an antibody to the pituitary gland which was demonstrated by an indirect immunofluorescence technique. Plain skull X-ray film and brain computerized tomography revealed an empty sella of the normal size. These results indicate the presence of partial deficiency of ACTH and prolactin, and that autoimmune disorders may be involved in the pathogenesis of her hypopituitarism.

Adrenocorticotropic Hormone↗
PubMed1986

A new case of abnormal insulinemia with diabetes. Reduced insulin values determined by radioreceptor assay.

A 44-yr-old Japanese woman was found to have diabetes with marked fasting hyperinsulinemia. Her fasting plasma glucose, serum insulin, and C-peptide levels were 137 mg/dl, 204 microU/ml, and 1.13 pmol/ml, respectively, and the C-peptide-to-insulin molar ratio was markedly reduced. Insulin antibodies and insulin-receptor antibodies were negative. Fasting levels of counter-insulin hormones were normal. She had normal hypoglycemic response to exogenous insulin injection. Binding of 125I-labeled insulin to erythrocytes was normal. Oral glucose-tolerance tests in eight members of her first-degree relatives revealed four members (mother, sister, brother, and daughter) with fasting hyperinsulinemia (111-314 microU/ml), and two of them (mother and sister) were overtly diabetic. Thus, the abnormality was thought to be an autosomal dominant trait. Reverse-phase high-performance liquid chromatograph analysis of immunopurified insulin obtained from her serum revealed two peaks of insulin immunoreactivity. The amount of the abnormal insulin peak was seven times greater than that of normal insulin. The abnormal insulin was eluted after bovine, human, and porcine insulins, indicating it has a more hydrophobic nature than normal human insulin. Radioreceptor assay (RRA) for serum insulin with guinea pig kidney membrane revealed that the binding activity of their serum insulin was markedly decreased. Discrepancies between the values measured by RRA and those measured by radioimmunoassay were also found in her family members with hyperinsulinemia but not in her family members without hyperinsulinemia and other hyperinsulinemic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Effects of bucumolol, a beta-adrenergic blocking agent, and its d-isomer on myocardial infarction produced by coronary artery ligation in rats.

Acute ligation of the left coronary artery of rats produced abnormal Q-wave in the electrocardiogram, tachycardia and frequent ventricular fibrillation. Serum CPK level was elevated, reaching a maximum at 3 to 5 hours after ligation and returning to near the pre-ligation level 24 hours later, when CPK activity in the left ventricle markedly decreased. Pretreatment with bucumolol at 2.5 mg/Kg s.c. and 5 mg/Kg s.c. lessened these changes and increased the survival rate in a dose related manner. d-Bucumolol at 5 mg/Kg, on the other hand, increased survival rate primarily by suppressing ventricular fibrillation without any significant effect on other parameters. These results suggest that the membrane stabilizing action does not contribute to protective actions of bucumolol against myocardial ischemia.

Adrenergic beta-Antagonists↗
PubMed1981

Cardiovascular pharmacology of bumepidil, a new synthetic vasoactive compound for coronary circulation.

Intravenously administered 8-tert.-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e]triazolo[1,5-alpyrimidine (bumepidil, CS-611) increased the coronary sinus outflow as well as intramyocardial flows in both subendocardial and subepicardial layers in the anesthetized dog and also the increase in the coronary arterial inflow was observed with short onset time, within 10 min when given orally to the conscious dog, and time for maximum effect is also short, i.e., 20 min after the oral administration. In the anesthetized rabbit flow-increase in the brain by CS-611 was next to the coronary, followed by the stomach and small intestines while there was no organ which showed a decreased flow. In the anesthetized open-chest dog cardiac output was increased by CS-611 while myocardial oxygen consumption was little affected. In addition, CS-611 exerted antiarrhythmic action on ventricular ectopics induced by coronary ligation of the conscious dog. A correlation between the increase in myocardial flow by CS-611 in the intact heart and the antiarrhythmic action in the coronary-lighted heart still remains to be studied further.

Animals↗
PubMed1980

Studies on cardiovascular agents. 6. Synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to heterocyclic systems.

The synthesis and coronary vasodilating and antihypertensive activities of 1,2,4-triazolo[1,5-a]pyrimidines fused to pyrrole, thiophene, pyran, pyridine, and pyridazine are described. Among these compounds, 8-tert-butyl-7,8-dihydro-5-methyl-6H-pyrrolo[3,2-e][1,2,4]triazolo[1,5-a]pyrimidine (23) was found to be the most promising potential cardiovascular agent, having been shown to be more potent in coronary vasodilating activity than trapidil [7-diethylamino)-5-methyl-1,2,4-triazolo[1,5-a]pyrimidine] and approximately equipotent to guanethidine sulfate in antihypertensive activity.

Animals↗
PubMed1980

Effects of CS-611 on the electrophysiological properties of canine cardiac tissues.

Effects of CS-611, a new coronary vasodilator, on the electrophysiological properties of Purkinje fibers, auricular and ventricular muscles isolated from dogs were examined with a microelectrodfe technique. CS-611 between 3 X 10(-6) and 3 X 10(-5) g/ml shortened the action potential duration (APD) of each tissue, especially of Purkinje fibers, without any significant alterations in the resting membrane potential, action potential amplitude and maximum rate of rise (V max). CS-611 also shortened the effective refractory period (ERP) of Purkinje fibers and ventricular muscles, but to a lesser extent than APD, resulting in an increase of ERP/ADP. The level of membrane potential needed to elicit premature excitation in Purkinje fibers and Vmax of the earliest response tended to increase in the presence of CS-611. CS-611 partially restored the reduced Vmax of Purkinje fibers exposed to hypoxia. The spontaneous firings in Purkinje fibers were decreased or abolished by CS-611. The possible role of these effects of CS-611 in its antiarrhythmic action was discussed.

Action Potentials↗
PubMed1975

Effects of beta blockers on cardiac function and myocardial oxygen consumption in the isolated supported heart preparation of the dog.

Effects of 2 different types of beta blockers, CS-359 and practolol, on mechanical performance and myocardial oxygen consumption (MVO2) in the isovolumic contraction of the isolated, blood-perfused canine heart with a support dog were studied. Two dose levels of the beta blockers were given intravenously to the support dog, one of which was enough to produce a significant beta adrenergic blocking action and other of which was a higher dose to reveal a direct depressant action on the isolated heart. CS-359 in the lower dose produced significant decreases in heart rate (HR), peak ventricular systolic pressure (peak VSP), and peak dp/dt while practolol caused no change in these parameters. The HR of the support dog was significantly decreased to the same degree in the lower dose of respective blocker. In the higher dose CS-359 decreased all parameters more definitely whereas practolol diminished peak VSP and peak dp/dt but did not significantly HR. MVO2 was decreased dose-relatedly by CS-359, but not affected significantly by practolol. From the analysis of relationships of MVO2 to peak VSP and HR in the isolated heart it is concluded that the effective reduction in MVO2 by CS-359 resulted mainly from a reduction in the peak VSP in the lower dose and additional decrease in HR in the higher dose of CS-359.

Adrenergic beta-Antagonists↗