Biomedical subjects

M Sakanashi

Publications and source records attributed to M Sakanashi.

At least 73 records · Page 4Linked to original sources

PubMed1989

Effects of beta-adrenoceptor blocking agents on isolated atrial and papillary muscles from experimentally diabetic rats.

Effects of propranolol and atenolol on isoproterenol-induced responses of isolated atrial and papillary muscles from experimentally diabetic rats were examined. Male Sprague-Dawley rats were divided into the diabetic group (DM) which received streptozotocin 60 mg/kg, i.v. and the control group (C) which received vehicle i.v. At 6 weeks after, the right atrial or right ventricular papillary muscle was isolated, and the beating rate (R) in the atrium or isometric force development (F) and its first derivatives (+/- dF/dt) in the papillary muscle under pacing were recorded. Basal R was less frequent in DM than in C, but ED50 values for isoproterenol-induced chronotropy were not different between the two groups. Basal F and basal +/- dF/dt were not different between the two groups, but isoproterenol-induced increases in F and +/- dF/dt were less in DM than in C. ED50 values in F and +dF/dt were not different between the two groups. Propranolol and atenolol shifted the concentration-response curves in R, F and +/- dF/dt for isoproterenol to the right in both groups. pA2 values of propranolol and atenolol for each parameter were not different between the two groups. Results indicate that propranolol and atenolol exert the same beta-adrenoceptor blocking potency in both diabetic and non-diabetic hearts of rats.

Animals↗

PubMed1989

Glutathione S-transferases and chloroform toxicity in streptozotocin-induced diabetic rats.

The glutathione S-transferase activity in liver and kidney cytosol was significantly decreased in short term diabetes induced with streptozotocin, whereas no decrease in the transferase was observed in phenobarbital-treated diabetic rats. Toxicity of chloroform was potentiated in streptozotocin- or phenobarbital-treated rats. The decrease in liver cytosolic and microsomal glutathione S-transferase activity was observed in long term diabetic rats, and only microsomal transferase activity was restored by insulin treatment. There was no release of glutathione S-transferases into the serum in the diabetic rats, and the transferases were not inhibited by streptozotocin in vitro. These results showed that glutathione S-transferase activity decreased during diabetes, and this decrease may contribute to altering drug metabolism and toxicity in diabetes.

Alanine Transaminase↗

PubMed1989

Investigation on the effect of dipyridamole and papaverine on regional blood flow and cardiac hemodynamics in anesthetized dogs.

Vasodilating effects of dipyridamole were compared with those of papaverine in anesthetized open-chest dogs. Dipyridamole i.v. produced a significant fall in aortic blood pressure and significant increases in aortic and coronary blood flows. Vertebral blood flow did not alter, but renal blood flow was transiently decreased. Left ventricular dP/dt, heart rate and left ventricular enddiastolic pressure were hardly affected by dipyridamole. Papaverine i.v. significantly increased aortic, vertebral and coronary blood flows, left ventricular dP/dt and heart rate and significantly decreased aortic blood pressure and left ventricular enddiastolic pressure. Renal blood flow was instantly decreased by papaverine. Percent change in each vascular resistance showed decreases in total peripheral, vertebral and coronary vascular resistances in response to both drugs, and the decrease in coronary vascular resistance was the most remarkable. Renal vascular resistance was increased by dipyridamole, while it was decreased by papaverine. Percent change in double product (heart rate x systolic arterial blood pressure) showed a monophasic decrease pattern with dipyridamole and a biphasic pattern with an initial, transient decrease followed by an increase with papaverine. The present results indicate that dipyridamole and papaverine produce marked coronary vasodilatation, and that papaverine is different from dipyridamole in cardiotonic properties.

Anesthesia↗

PubMed1989

Effects of dobutamine and acetylcholine on perfused hearts isolated from streptozocin-induced diabetic rats.

In order to study the responsiveness of the diabetic heart to autonomic agents, effects of dobutamine (DOB) and acetylcholine (ACh) on perfused hearts isolated from streptozocin (streptozotocin, STZ)-induced diabetic rats and insulin-treated diabetic rats were evaluated. Male Sprague-Dawley rats, weighing 180-210 g, were divided into control (C) group, diabetes mellitus (DM) group, and diabetes mellitus treated with insulin (DMI) group. C group was injected with buffered vehicle. DM and DMI groups were injected intravenously with 60 mg/kg STZ at the first day. Three days after STZ injection, DMI group was subsequently treated with 4 U of insulin zinc suspension (lente insulin) subcutaneously every day. At 45 days after injection of STZ, experiments were performed using a Langendorff perfused heart preparation. In the evaluation of effect of ACh, heart rate and myocardial developed tension (T) were measured. In the evaluation of effect of DOB, heart was paced at 300 beats/min and T was measured isometrically. Plasma glucose values (mg/dl) were 116.0 +/- 4.9 in C, 482.3 +/- 30.3 in DM, and 204.6 +/- 34.8 in DMI group, respectively. The order of percent increases in T induced by DOB (10(-8)-3 x 10(-6) g) was C greater than DMI greater than DM. The order of percent decreases in T and heart rate by ACh (10(-7)-3 x 10(-6) g) was C greater than DMI greater than DM. These results suggest that both adrenergic receptor-mediated and cholinergic receptor-mediated cardiac responsiveness are significantly depressed in the diabetic heart.

Acetylcholine↗

PubMed1988

Effects of atenolol and some other beta-adrenoceptor blocking agents on norepinephrine-induced responses in isolated and perfused rat hearts.

The effects of atenolol and another three beta-adrenoceptor blocking agents on norepinephrine (NE)-induced cardiac responses were examined in isolated and perfused rat hearts following a Langendorff method. Bolus injection of atenolol did not show significant inhibitory effects on NE-induced increases in myocardial contractile force (MCF) and heart rate. Bolus injections of metoprolol and timolol were also ineffective for inhibiting NE-responses. However, both bolus injection and infusion of propranolol or infusion of atenolol, metoprolol and timolol all significantly inhibited NE-responses. On sustained increase in MCF induced by infusion of NE, the inhibitory effect of atenolol was transient, while that of propranolol was continuous. From these results, it is concluded that atenolol displays a different time course of action on NE-induced cardiac responses by bolus injection or infusion because of its pharmacological properties, which may be due to its low lipophilicity.

Adrenergic beta-Antagonists↗

PubMed1988

Cardiovascular effects of the new calcium antagonist isradipine and of diltiazem in anesthetized open-chest dogs.

Cardiovascular effects of the new calcium antagonist, isradipine (PN 200-110), were compared with those of diltiazem in anesthetized open-chest dogs. Isradipine 5 micrograms/kg i.v. produced significant decreases in systolic, diastolic and mean aortic blood pressure (AoP) concomitant with a decrease in mean renal blood flow (RBF) and increases in mean vertebral blood flow (VBF), mean coronary blood flow (CBF) and left ventricular dP/dt (LVdP/dt), but almost unchanged heart rate (HR) and left ventricular enddiastolic pressure (LVEDP). Diltiazem 300 micrograms/kg i.v. also produced decreases in AoP and RBF and increases in AoF, VBF and CBF. LVdP/dt and LVEDP were not significantly changed, but HR was decreased by this drug. Duration of increase in AoF, VBF and CBF was significantly longer in isradipine than in diltiazem. The decrease of coronary vascular resistance relative to total peripheral resistance was significantly greater than 1.0 for diltiazem, but not for isradipine. Results indicate that isradipine produces effects on AoP, AoF, VBF, CBF, RBF and LVEDP similar to diltiazem and the drug increases LVdP/dt without a decrease in HR in contrast to diltiazem, and that the effects of isradipine were long sustained when compared with those of diltiazem.

Anesthesia↗

PubMed1987

Effects of intracoronary propranolol on coronary blood flow and regional myocardial function in dogs.

The study was conducted to evaluate the effects of intracoronary administration of dl-propranolol on coronary blood flow and regional myocardial function in anesthetized open-chest dogs. The results were compared with those obtained with d-propranolol, atenolol and lidocaine. Bolus intracoronary injections of dl-propranolol (0.02-2 mg) dose dependently produced transient increases in coronary blood flow and subsequent depression in regional segment shortening which qualitatively resembled those produced by the dextro isomer (0.02-2 mg) and lidocaine (0.2-10 mg). Atenolol (up to 2 mg) was almost devoid of these effects. Isoproterenol-induced responses were abolished by dl-propranolol and atenolol but only incompletely blocked by d-propranolol. These results demonstrate that propranolol at high doses has direct coronary vasodilating and cardiodepressant effects in situ, and indicate that the major part of these effects can be attributed to the membrane-stabilizing action rather than beta-adrenoceptor blockade.

Animals↗

PubMed1987

Effects of nipradilol on myocardial ischaemia produced by coronary stenosis in dogs.

Effects of nipradilol which is a new beta-adrenoceptor blocking agent endowed with nitroglycerin-like vasodilator actions, its denitrated derivative (denitro nipradilol) and propranolol on abnormalities of regional myocardial shortening produced by partial occlusion of the left circumflex coronary artery (LCX) were studied in anaesthetized open-chest dogs. In the presence of LCX stenosis, nipradilol (0.1 mg kg-1, i.v.) produced marked decreases in heart rate and LVdP/dt without a significant increase in left ventricular end-diastolic pressure (LVEDP). It improved impaired myocardial segment shortening and restored normal cardiac lactate metabolism. Denitro nipradilol (0.2 mg kg-1 i.v.) and propranolol (0.2 mg kg-1 i.v.) both caused similar haemodynamic changes to nipradilol but also produced a significant increase in LVEDP. However, improvement by these two agents of regional dysfunction in the ischaemic myocardium was comparable to those seen with nipradilol. All three agents markedly inhibited isoprenaline-induced tachycardia, but vehicle did not. Atrial pacing abolished the beneficial effect of nipradilol on myocardial shortening in the ischaemic region without affecting other haemodynamic parameters. These results indicate that nipradilol alleviates acute myocardial ischaemia produced by coronary stenosis with similar efficacy to denitro nipradilol and propranolol suggesting, that a major part of the beneficial effect of nipradilol may be attributable to its beta-adrenoceptor blocking action.

Adrenergic alpha-Antagonists↗

PubMed1987

Responses of renal, coronary and vertebral vasculatures to MC-838 and captopril in anesthetized dogs.

The regional hemodynamic effects of MC-838, a new angiotensin-converting enzyme inhibitor, and captopril at equidepressor doses were examined in the anesthetized dog by simultaneously measuring renal (RBF), coronary (CBF), vertebral (VBF) arterial and aortic blood flow (AoF). Hemodynamic responses to angiotensin I (AI), AII and noradrenaline were compared before and after the administration of each inhibitor. MC-838 (3 mg/kg i.v.) lowered gradually aortic pressure (AoP) and increased moderately AoF and RBF up to 60 min after the administration. Captopril (0.1 mg/kg i.v.) lowered AoP immediately after the administration and increased AoF and RBF more shortly than MC-838. Neither inhibitor produced a marked change in VBF or CBF. The effects of the inhibitors in the renal vascular bed was much greater than that in vertebral and coronary vascular beds, although vascular resistance in all of them was significantly reduced. Each of the drugs inhibited the pressor and renal vasoconstrictor responses to AI. These results indicate that the renal vasculature is more sensitive to both MC-838 and captopril than vertebral and coronary vasculature, but MC-838 has a slower and longer-lasting action than does captopril.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

An analysis of the depressant effect of indomethacin on contractions of isolated and perfused rat hearts.

The depressant effect of indomethacin on contractions of isolated rat hearts was investigated under a constant heart rate. Ca2+ produced dose-dependent increases in myocardial contractile force and coronary perfusion pressure. Indomethacin-infusion significantly decreased myocardial contractile force and depressed increases in myocardial contractile force by Ca2+, but never affected both coronary perfusion pressure and increases in coronary perfusion pressure by Ca2+. Results suggest that indomethacin will depress myocardial contractile force with no involvement of any calcium antagonism.

Animals↗

PubMed1987

Effects of adrenergic drugs on isolated and perfused hearts of streptozotocin-induced diabetic rats.

To examine the myocardial contractile response of the diabetic heart, effects of isoproterenol (ISO) and norepinephrine (NE) on perfused hearts isolated from streptozotocin (STZ)-induced diabetic rats and insulin-treated diabetic rats were evaluated. Male Sprague-Dawley rats, weighing 200-260 g, were divided into the control (C)-group, diabetes mellitus (DM)-group and diabetes mellitus treated with insulin (DMI)-group. The C group was injected with buffered vehicle. DM and DMI groups were injected intravenously with 60 mg/kg STZ on the first day. Three days after STZ injection, the DMI group was subsequently treated with 4 U of Lente insulin subcutaneously every day. At 45 days after injection of STZ, experiments were performed using a Langendorff perfused heart preparation. The heart was paced at 300 beats/min, and myocardial developed tension (T) was measured isometrically. Plasma glucose values (mg/dl) were 142.4 +/- 8.7 in C, 499.3 +/- 15.6 in DM and 370.6 +/- 27.6 in DMI group. The order of percent increase in T induced by ISO (3 X 10(-9) - 3 X 10(-8) g) was C = DMI much greater than DM, and that by NE (10(-7) - 10(-6) g) was C greater than DMI greater than DM. On the other hand, the percent increase in T induced by CaCl2 (1.1 X 10(-4) - 2.2 X 10(-3) g) and aminophylline (AMI, 0.31 X 10(-3) - 5.00 X 10(-3) g) was not significantly different among three groups. These results indicate that adrenergic receptor-mediated contractile response was significantly depressed in the diabetic heart.

Aminophylline↗

PubMed1987

Effects of Chrysanthemum indicum Linn. on coronary, vertebral, renal and aortic blood flows of the anesthetized dog.

The hemodynamic effects of the water extract of flower of Chrysanthemum indicum Linn. (CIL) and adenosine were examined in anesthetized open-chest dogs by measuring simultaneously and continuously coronary (CBF), vertebral (VBF), renal (RBF) and aortic blood flows (AoF). Intravenous administration of CIL (5-20 mg/kg) as well as adenosine (10-50 micrograms/kg) produced decreases in aortic blood pressure (AoP) and RBF, and increases in AoF, VBF, CBF and left ventricular dP/dt (LVdP/dt). Calculated coronary, vertebral and total peripheral resistances were decreased by CIL or adenosine in a dose-dependent manner. The ratio (1.69 +/- 0.27) of decrease in coronary vascular resistance to that in total peripheral resistance by CIL (10 mg/kg) was apparently smaller than that (4.03 +/- 0.48) by adenosine (10 micrograms/kg). After beta-adrenergic blockade, increases in AoF and LVdP/dt were inhibited, but decreases in AoP and coronary, vertebral and total peripheral resistances and increase in renal vascular resistance were not changed. These results indicate that CIL directly and uniformly produces coronary and systemic vasodilation with renal vasoconstriction, and that adenosine directly produces vasoconstriction in renal vasculature and vasodilation which is more potent in coronary vasculature than in systemic ones.

Adenosine↗

PubMed1986

Vasodilating effects of nicorandil and nitroglycerin in anaesthetized open-chest dogs.

Vasodilating effects of intravenous administrations of nicorandil (SG-75) and nitroglycerin were analyzed in anaesthetized open-chest dogs by measuring simultaneously, and continuously, coronary (CBF), vertebral (VBF), renal (RBF) and aortic blood flow (AoF). Nicorandil 10-300 micrograms/kg i.v. and nitroglycerin 1-30 micrograms/kg i.v. decreased aortic blood pressure and increased CBF in a dose-dependent fashion. The doses of nicorandil and nitroglycerin which reduced coronary vascular resistance to about 60% of the predrug value were 100 micrograms/kg and 10 micrograms/kg, respectively. Nicorandil 100 micrograms/kg i.v. significantly increased AoF and heart rate, significantly decreased left ventricular end-diastolic pressure and did not significantly change VBF, RBF and left ventricular dP/dt. Nitroglycerin 10 micrograms/kg i.v. significantly increased VBF and heart rate, significantly decreased left ventricular end-diastolic pressure and produced an initial increase followed by a decrease in AoF and RBF. When compared with these doses of both drugs, the ratio of percent decrease in coronary vascular resistance to that in total peripheral resistance was over 1.0 in both drugs and the value of this ratio in nicorandil was significantly larger than that in nitroglycerin. The duration of increase in CBF produced by nicorandil 10-300 micrograms/kg i.v. was dose-dependent, but was not changed by nitroglycerin 1-30 micrograms/kg i.v. The results indicate that nicorandil and nitroglycerin dilate coronary vasculature more markedly than other vascular beds and that the potency of selective coronary vasodilatation and the duration of action are more significant in nicorandil than in nitroglycerin.

Anesthesia↗

PubMed1986

Effects of habu (Trimeresurus flavoviridis) venom on isolated and perfused hearts of rats.

Crude habu venom decreased coronary perfusion pressure and produced a small increase in myocardial tension of isolated and perfused rat hearts. Indomethacin infusion depressed the fall in perfusion pressure caused by the venom, without affecting the increase in tension. Heated venom decreased perfusion pressure, but did not increase myocardial tension. These results suggest that crude habu venom has coronary vasodilating and positive inotropic effects, possibly through actions of a phospholipase A2 and a heat-labile component, respectively.

Animals↗

PubMed1986

Comparative effects of diltiazem and glycerol trinitrate on isolated ureter and coronary artery of the dog.

Effects of diltiazem on isolated ureter and coronary artery of the dog were compared with those of glycerol trinitrate (GTN). Diltiazem (DZ) (10(-9)-10(-6) M) decreased the force and frequency of ureteral rhythmic contractions evoked by potassium or phenylephrine in a concentration-dependent manner, and relaxed potassium-contracted coronary artery strips. The dose dependence of the inhibitory effects of diltiazem was similar on the ureter and coronary artery. GTN (10(-7)-10(-5) M) also showed similar inhibitory effects, but these were more pronounced on the coronary artery than on the ureter.

Animals↗

PubMed1986

Comparison of acute hemodynamic effects of MC-838, a new angiotensin-converting enzyme inhibitor, with captopril in anesthetized dogs.

Effects of a new angiotensin-converting enzyme inhibitor, N-[3-(N-cyclohexanecarbonyl-D-alanylthio)-2-methylpropanoyl] -L-proline calcium (MC-838), on the systemic and coronary circulation were evaluated in anesthetized dogs, and the effects were compared with those of captopril. Administration of MC-838 (0.1, 0.3, 1.0 and 3.0 mg/kg, i.v.) produced a gradual and dose-dependent decline in aortic pressure associated with no marked changes in coronary blood flow, heart rate and LVdP/dt. Captopril (0.01, 0.03, 0.1 and 0.3 mg/kg, i.v.) also caused a dose-related decrease in aortic pressure, but the significant hypotension appeared more rapidly than that of MC-838. Both MC-838 and captopril inhibited selectively the pressor response to angiotensin I in a dose-related manner. The doses of MC-838 and captopril to lower mean aortic pressure by 10 mmHg from the pre-drug value were 2.8 mg/kg and 0.03 mg/kg, respectively; those of these drugs to cause 50% inhibition of angiotensin I-pressor response were 1.0 mg/kg and 0.04 mg/kg, respectively. When administration of MC-838 (3.0 mg/kg) was repeated three times at a 30 min-interval, the second and third injections caused no additional hypotension, while each of the repeated injections of captopril (0.3 mg/kg) produced significant hypotension. These results indicate that MC-838 inhibits angiotension I-conversion and decreases systemic blood pressure more slowly and persistently than captopril in anesthetized dogs.

Anesthesia↗

PubMed1986

Possible involvement of ganglionic blocking effects of diltiazem in regulation of blood pressure and heart rate of the rabbit.

Under pentobarbitone anesthesia, arterial blood pressure and heart rate were recorded in rabbits. The elevation in systemic blood pressure and increased heart rate induced by electrical stimulation of the right thoracic sympathetic nerve trunk were depressed by either an intravenous injection of diltiazem (300 micrograms/kg) or by placing cotton pledgets soaked in 2 mM diltiazem solution onto the right stellate ganglion. These inhibiting effects of diltiazem were statistically significant with high sympathetic stimulation frequencies (10-20 Hz), but not when lower frequencies (1-5 Hz) were used. On the other hand, hexamethonium (10 mg/kg i.v. or 100 mM applied topically) depressed cardiovascular responses to sympathetic stimulation over a wide range of frequencies (1-20 Hz). Present results reveal a frequency-dependent inhibition of ganglionic transmission by diltiazem, and suggest that diltiazem may depress excessive sympathetic activity without affecting normal ganglionic transmission.

Animals↗

PubMed1986

Acute effects of bunazosin on aortic, vertebral, coronary and renal blood flows of anesthetized dogs.

Effects of 4-amino-2-(4-butyrylhexahydro-1H-1,4-diazepin-1-yl)-6,7-dime thoxy-quinazoline (bunazosin, E-643, Detantol) on aortic, vertebral, coronary and renal blood flows were investigated in anesthetized open-chest dogs. Bunazosin 1, 10 and 100 micrograms/kg i.v. dose-dependently decreased aortic blood pressure (AoP) and inhibited the increase in AoP by phenylephrine 5 micrograms/kg i.v. However, the increase in AoP by norepinephrine 0.5 microgram/kg i.v. remained even after bunazosin 100 micrograms/kg i.v. and was almost undetectable after additional administration of yohimbine 1000 micrograms/kg i.v. A hypotension by bunazosin persisted more than 15 min, but dose-dependent increases in heart rate (HR) induced by bunazosin 1, 10 and 100 micrograms/kg i.v. restored within 2 min. Bunazosin 100 micrograms/kg i.v. significantly but transiently increased aortic blood flow and decreased renal blood flow. Vertebral and coronary blood flows were not significantly changed. Left ventricular dP/dt was transiently increased. Calculated total peripheral vascular resistance and coronary vascular resistance were transiently but significantly decreased. No significant changes were observed in both vertebral vascular resistance and renal vascular resistance. The results indicate that bunazosin maintains the blood flows to brain, heart and kidney, and is continuously lowering AoP without significant changes in HR.

Adrenergic alpha-Antagonists↗