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Biomedical subjects

A Narimatsu

Publications and source records attributed to A Narimatsu.

At least 37 records · Page 2Linked to original sources
PubMed1990

A study on follicle stimulation and ovulation induction in polycystic ovary syndrome (PCOS).

The present study was undertaken to verify the efficacy of preparations for inducing follicular maturation and ovulation in patients with polycystic ovary syndrome (PCOS). Successful induction of ovulation in patients with PCOS was observed in treatment cycles with daily injections or pulsatile subcutaneous administration of human menopausal gonadotropin (hMG), the combination of clomiphene citrate and bromocriptine, or the combination of clomiphene citrate and hMG. The incidence of ovarian hyperstimulation syndrome varied with the different clinical conditions in which ovulation was induced, the types of preparations administered, and the doses and schedules administered.

Bromocriptine↗
PubMed1990

[Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on ischemic myocardial energy and carbohydrate metabolism in dogs].

The effect of betaxolol, a beta 1-adrenoceptor antagonist, on ischemic myocardial metabolism was studied in dog hearts subjected to an occlusion of the left anterior descending coronary artery for 10 or 30 min. Betaxolol (0.1 or 0.3 mg/kg) was injected i.v. 5 min before ischemia. Betaxolol decreased heart rate, (+)dp/dt, coronary flow and blood pressure. Coronary occlusion decreased the levels of creatine phosphate, adenosine triphosphate, total adenine nucleotides and energy charge potential in the ischemic myocardium. Ten minutes after ischemia, betaxolol significantly diminished these impairments of energy metabolism. Even 30 min after ischemia, a higher dose of betaxolol significantly inhibited the depletion of total adenine nucleotides. Myocardial ischemia produced a breakdown of glycogen, an accumulation of lactate and an inhibition of glycolytic flux through the phosphofructokinase reaction. Betaxolol also reduced these alterations of carbohydrate metabolism 10 min after ischemia. These results indicate that betaxolol delays the onset of myocardial metabolic change from aerobic to anaerobic during ischemia and hence reduces the severity of myocardial ischemic injury.

Adenine Nucleotides↗
PubMed1990

[Antihypertensive effect of betaxolol, a cardioselective beta-adrenoceptor antagonist, in experimental hypertensive rats].

Betaxolol is a highly selective beta 1-adrenoceptor antagonist without intrinsic sympathomimetic activity. In this study, the antihypertensive effect of betaxolol was investigated in experimental hypertensive rats; and the antihypertensive mechanism was also studied. Betaxolol (1 and 10 mg/kg, p.o.) produced acute hypotensive effects in conscious spontaneously hypertensive rats (SHR), renal hypertensive rats, deoxycorticosterone/saline hypertensive rats and normotensive rats. The effect was particularly marked in SHR. Furthermore, daily oral administration of betaxolol to SHR for 3 weeks showed sustained antihypertensive effects without producing tolerance. In pithed rats, the pressor response induced by an electrical stimulation of the spinal cord was inhibited by both betaxolol and atenolol. However, only betaxolol reduced the pressor response to norepinephrine. These findings suggest that a certain relaxing effect on peripheral vascular beds in addition to inhibition of presynaptic beta-adrenoceptors may contribute to the antihypertensive mechanism of betaxolol.

Administration, Oral↗
PubMed1990

[Antihypertensive effect of betaxolol, a cardioselective beta-adrenoceptor antagonist, in renal hypertensive dogs].

The antihypertensive effect of betaxolol, a highly selective beta 1-adrenoceptor antagonist, was investigated in renal hypertensive dogs, and the mechanism was also studied. A single oral administration of betaxolol (1 and 10 mg/kg) lowered blood pressure dose-dependently. The hypotensive effect of betaxolol was enhanced by daily oral administration for 10 days. In anesthetized dogs, intraarterial injection of betaxolol produced a dose-dependent increase in femoral artery flow; and in this test, betaxolol was 3 times less potent than papaverine. The increase in blood flow with betaxolol was not affected by pretreatment with propranolol. These findings indicate that a certain vasodilating activity may contribute to the antihypertensive mechanism of betaxolol.

Adrenergic beta-Antagonists↗
PubMed1990

Betaxolol, a cardioselective beta-adrenoceptor antagonist, attenuates ischemic myocardial acidosis in dogs.

The effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on ischemic myocardial acidosis were studied in dog hearts, in which the left anterior descending coronary artery was partially occluded for 90 min, and were compared with those of atenolol and propranolol. Myocardial ischemia produced a decrease in myocardial pH (measured by a micro glass pH electrode) and an elevation of the ST segment of epicardial ECG (assessed by a surface electrode). Betaxolol (0.01, 0.03 or 0.1 mg/kg), atenolol (0.03 or 0.1 mg/kg) or propranolol (0.03 or 0.1 mg/kg), when injected i.v. 30 min after ischemia, restored myocardial pH and the ST segment of ECG that had been altered by partial occlusion. However, the effect of betaxolol on myocardial acidosis was more potent than that of atenolol or propranolol. The decrease in (+)dp/dt by betaxolol (0.03 mg/kg) was less potent than that by atenolol (0.1 mg/kg) and equivalent to that by propranolol (0.1 mg/kg), although the restorations of myocardial acidosis by the drugs were almost equivalent. These results have confirmed that beta-adrenoceptor antagonists attenuate the ischemia-induced myocardial acidosis and have shown that among three beta-adrenoceptor antagonists, betaxolol is the most effective in improving myocardial acidosis with a relatively weak effect on myocardial contractile function.

Acidosis↗
PubMed1990

Effects of betaxolol on cardiohemodynamics and coronary circulation in anesthetized dogs: comparison with atenolol and propranolol.

Effects of betaxolol, a cardioselective beta-adrenoceptor antagonist, on cardiohemodynamics and coronary circulation were investigated in two kinds of anesthetized open-chest dog preparations in comparison with those of atenolol and propranolol. When administered intravenously, betaxolol, atenolol and propranolol produced dose-dependent decreases in the heart rate (HR), maximum left ventricular dP/dt [+)dP/dt), cardiac output (CO) and mean arterial pressure (MAP). Although all three drugs were almost equipotent in decreasing HR, betaxolol was much less potent than atenolol and propranolol in decreasing (+)dP/dt. Betaxolol decreased the total peripheral resistance (TPR), whereas atenolol and propranolol increased it. In another series of experiments, when administered intravenously, betaxolol, atenolol and propranolol all produced a decrease in the myocardial oxygen consumption (MVO2) and an increase in the atrioventricular conduction time (AVCT). All three drugs were nearly equipotent in decreasing MVO2, although betaxolol was less potent than the other two drugs at higher doses (greater than 300 micrograms/kg). Prolongation of AVCT with propranolol was stronger than those with betaxolol and atenolol. These results suggest that, unlike atenolol and propranolol, the decrease in TPR as well as beta 1-adrenoceptor blockade may be responsible for both the hypotensive effect of betaxolol and the decrease in MVO2 with betaxolol. The result that the cardiodepressant effect of betaxolol was much less potent than those of atenolol and propranolol suggests that betaxolol would be more beneficial than the others in the treatment of ischemic heart disease.

Animals↗
PubMed1990

[CT findings of the benign tracheobronchial lesions with calcification].

In the benign tracheobronchial lesions with calcification, tracheobronchopathia osteochondroplastica, relapsing polychondritis and tracheobronchial amyloidosis were considered. CT demonstrated small nodules with calcifications at the trachea with or without deformity of tracheal wall in the case of tracheobronchopathia osteochondroplastica, swelling of tracheal cartilage with diffuse and multiple calcifications in the case of relapsing polychondritis and calcifications in the deep parts of tracheobronchial amyloid nodules. CT findings were able to differentiate those benign lesions. High-resolution CT is more useful in the distribution of abnormal calcification of these diseases.

Aged↗
PubMed1989

In vitro characterization of the effects of MCI-154, a novel cardiotonic agent, on cardiac tissues.

In vitro cardiac effects of a cardiotonic drug, MCI-154, for which the main action mechanism was proposed to be the enhancement of Ca2+ sensitivity of cardiac contractile proteins, were investigated. MCI-154 (3 x 10(-8)-3 x 10(-4) M) increased the developed tension in isolated ventricular muscles from cats, dogs, guinea pigs and rats and increased that of isolated left atrial muscles of guinea pigs and rats. However, species differences were observed in the responses to MCI-154. The positive inotropic potency of MCI-154 was stronger than those of amrinone and milrinone. In the isolated right atria from guinea pigs and rats, properties of the chronotropic effect of MCI-154 were different from those of amrinone and milrinone. The positive inotropic action of MCI-154 was not affected by phentolamine, propranolol, cimetidine and tetrodotoxin. MCI-154 did not inhibit cardiac Na+,K+-ATPase. MCI-154 moderately stimulated Ca2+-uptake of isolated cardiac sarcoplasmic reticulum (SR), but induced no release of Ca2+ from the SR. These results support the view that the main mechanism for the action of MCI-154 is the enhancement of Ca2+ sensitivity of cardiac contractile proteins.

Amrinone↗
PubMed1989

Comparison of the effects of MCI-154, a new cardiotonic agent, and some Ca2+-sensitizing agents on the response of the contractile system to Ca2+ in skinned cardiac muscle.

Several cardiotonic agents (MCI-154, sulmazole, pimobendan and adibendan) were examined for their ability to influence Ca2+-activated tension development and MgATP-activated tension development in the absence of free Ca2+ (rigor tension), using the chemically skinned fiber from guinea pig papillary muscles. MCI-154, sulmazole, pimobendan and adibendan all increased the tension development induced by pCa (-log[Ca2+]M) 5.8 in a concentration-dependent manner (10(-6) to 10(-4) M). The order of the potency was as follows: MCI-154 greater than pimobendan greater than adibendan greater than sulmazole. MCI-154 enhanced the maximum tension developed at pCa 4.4 but sulmazole, pimobendan and adibendan did not enhance it. MCI-154, but not sulmazole, pimobendan and adibendan, enhanced the tension development induced by pMgATP (-log[MgATP]M) 6.0 in the absence of free Ca2+. MCI-154, sulmazole, pimobendan and adibendan concentration-dependently (10(-7) to 10(-4) M) increased the force of contraction in isolated guinea pig papillary muscles. The order of the potency was as follows: MCI-154 greater than adibendan greater than pimobendan greater than sulmazole. These results demonstrated that the Ca2+-sensitizing action on the contractile system may be involved in the positive inotropic action of MCI-154, sulmazole, pimobendan and adibendan, and that MCI-154 is the most potent among these drugs. Furthermore, sulmazole, pimobendan and adibendan did not enhance the interaction of actin and myosin, suggesting that the mechanism of actions of these drugs are qualitatively different from that of MCI-154.

Adenosine Triphosphate↗
PubMed1989

Potent stimulation of myofilament force and adenosine triphosphatase activity of canine cardiac muscle through a direct enhancement of troponin C Ca++ binding by MCI-154, a novel cardiotonic agent.

In the present study we have analyzed a likely biochemical mechanism underlying the Ca++-sensitizing action of MCI-154 (6-[4-(4'-pyridyl)aminophenyl)-4,5-dihydro-3(2H)-pyridazinone hydrochloride), a novel cardiotonic agent, on the contractile protein system. MCI-154 (10(-7) to 10(-4) M) enhanced the tension development induced by -log molar-free Ca++ concentration (pCa) 5.8 in chemically skinned fiber from the canine right ventricular muscle in a concentration-dependent manner. At pCa 7.0, MCI-154 (10(-7) to 10(-4) M) markedly increased adenosine triphosphatase (ATPase) activities of canine myofibrils and reconstituted actomyosin. In myofibrils and reconstituted actomyosin, MCI-154 (10(-7) to 10(-4) M) caused a parallel shift of the pCa-ATPase activity relation curve to the left without affecting the maximum activity, suggesting an increase in Ca++ sensitivity. MCI-154 (10(-8) to 10(-4) M) had little effect on actin-activated, Mg++, Ca++ and (K+, EDTA)-ATPase activities of myosin. Ca++ binding to cardiac myofibrils or purified cardiac troponin was increased by 10(-4) M MCI-154. These results suggest that MCI-154 enhances Ca++ binding to cardiac troponin C to elevate the Ca++ sensitivity of myofilaments and thus may cause a positive inotropic action in cardiac muscle. MCI-154 may provide a valuable tool for studying the molecular mechanism by which Ca++ regulates the contractile system.

Actin Cytoskeleton↗
PubMed1988

[Effects of terazosin on the blood pressure responses to tilting in conscious animals: comparison with prazosin].

Inhibitory effects of terazosin on the compensatory blood pressure responses to tilting were studied in conscious rabbits and spontaneously hypertensive rats (SHR). In rabbits, doses which reduced the mean blood pressure by 15 mmHg were 330 micrograms/kg, i.v., for terazosin and 42 micrograms/kg, i.v., for prazosin, while those which depressed the blood pressure responses to tilting by 30 mmHg were 180 micrograms/kg, i.v., for terazosin and 54 micrograms/kg, i.v., for prazosin. In SHR, almost equal decreases in the mean blood pressure (about 30%) were observed by 1 mg/kg prazosin, p.o., 20 mg/kg hexamethonium, i.p., 3 mg/kg hydralazine, p.o., or 3 mg/kg nicardipine, p.o. In these conditions, prazosin and hexamethonium markedly depressed the blood pressure responses to tilting, whereas hydralazine and nicardipine showed little effect. The results with these antihypertensive drugs closely paralleled the established orthostatic profiles seen clinically. In this SHR tilting model, when the mean blood pressure was reduced by 15%, prazosin significantly depressed the tilting reflexes; however, terazosin produced no depression. Considering the dose ratio of terazosin to prazosin for antihypertensive effects and inhibitory effects on the tilting reflexes, the orthostatic liability of terazosin was about 3 times as low as that of prazosin. On the basis of these results, it is expected that terazosin causes less orthostatic hypotension than prazosin in clinical use.

Adrenergic alpha-Antagonists↗
PubMed1987

Contractile proteins: possible targets for the cardiotonic action of MCI-154, a novel cardiotonic agent?

The effect on the contractile protein system of MCI-154, a novel and potent cardiotonic agent, was examined by using thin bundles of chemically skinned fibers from the guinea-pig papillary muscles. MCI-154 increased the Ca2+ sensitivity of the contractile protein system of the cardiac skinned fibers. Moreover, MCI-154 enhanced the maximum tension developed at pCa 4.4. These results suggest that an increase in responses of the contractile protein system to Ca2+ ion is, at least in part, responsible for the positive inotropic action of MCI-154.

Animals↗
PubMed1987

A novel class of cardiotonics. Synthesis and pharmacological properties of [4-(substituted-amino)phenyl]pyridazinones and related derivatives.

A series of [4-(substituted-amino)phenyl]pyridazinones and [4-(substituted-methyl)amino]phenyl]pyridazinones was synthesized and evaluated for inotropic activity in vitro and for cardiohemodynamic effects in vivo. Above all, 6-[4-(4-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride (4, MCI-154) and 6-[4-(4-pyridylamino)phenyl]-5-methyl-4,5-dihydro-3(2H)-pyridazinone hydrochloride (5) showed extremely potent positive inotropic activity along with vasodilating activity. Regarding dP/dtmax (an indicator for cardiac contractility), ED30's (doses that increased dP/dtmax by 30%) of compounds 4 and 5 were 8.5 +/- 1.9 and 4.4 +/- 0.6 micrograms/kg, respectively, where that of amrinone was 471.9 +/- 94.1 micrograms/kg. Structure-activity relationships of these series are presented, and a plausible model of receptor binding is discussed.

Animals↗
PubMed1987

Use of bromocriptine in the treatment of normoprolactinemic infertility.

The efficacy of bromocriptine therapy was studied in 84 normoprolactinemic infertile patients. Bromocriptine (2.5-5.0 mg/day) was given for at least 1 month. Bromocriptine therapy was effective in 54 of 84 cases (64%), including 6 of 15 (40%) cases with amenorrhea, 16 of 24 cases (67%) with anovulatory cycle, 9 of 15 cases (60%) with delayed ovulation and 23 of 30 cases (77%) with luteal phase defect. Sixteen cases were able to conceive with bromocriptine alone. Twenty-five patients who did not respond to bromocriptine were treated with a combination therapy consisting of bromocriptine and clomiphene. Of the 25 cases, 14 responded to the therapy, and 6 of them were able to conceive. The response of prolactin to domperidone (10 mg, i.v.) was significantly (p less than 0.01) higher in the group responding to bromocriptine than in the nonresponding group. These results indicate that the administration of bromocriptine is an effective therapy for patients with normoprolactinemic endocrine disorders, and that domperidone may be useful in selecting the candidates for bromocriptine therapy.

Adult↗
PubMed1987

Changes in membrane potentials and currents of ventricular cells of the guinea pig heart by a new cardiotonic drug, MCI-154.

Effects of MCI-154, a newly synthesized cardiotonic drug with vasodilator property, on the membrane potential and currents of the isolated papillary muscles and the single ventricular cells of the guinea pig were examined. MCI-154 (10(-7)-10(-4) M) increased the developed tension in a dose-dependent manner without significant changes in the action potential configuration of the guinea pig papillary muscle. The slow response action potential obtained by increasing the extracellular K+ concentration to 24 mM was augmented by MCI-154 (10(-6) and 10(-4) M). This effect of MCI-154 was not blocked by atenolol (10(-6) M). In voltage clamp experiments on single ventricular cells, the slow inward current was not affected, but the inward rectifier K+ current was reduced by higher concentration of MCI-154 (10(-4) M). Considering the "run down" phenomenon of the slow inward current, the possibility that MCI-154 might have a slight increasing effect on the slow inward current could not be ruled out. From these results, it can be concluded that the positive inotropic action of MCI-154 can be explained partially by the decrease in the inward rectifier K+ current, and probably by the increase in the Ca2+ sensitivity of the contractile protein system.

Action Potentials↗