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Biomedical subjects

M Sakanashi

Publications and source records attributed to M Sakanashi.

At least 91 records · Page 5Linked to original sources
PubMed1986

Comparison of vasodilating effects of nisoldipine and nifedipine in anesthetized open-chest dogs.

Hemodynamic effects of nisoldipine (Bay k 5552) were compared with those of nifedipine in anesthetized open-chest dogs. Both nisoldipine and nifedipine produced a fall in aortic pressure and increases in aortic, vertebral and coronary blood flows. After administration of nisoldipine, renal blood flow, heart rate and left ventricular enddiastolic pressure were not changed, but left ventricular dP/dt was increased. After administration of nifedipine, renal blood flow and left ventricular dP/dt were decreased, and left ventricular enddiastolic pressure was elevated. Heart rate was hardly changed. Durations of increases in aortic, vertebral and coronary blood flows were about 3 times longer after nisoldipine than after nifedipine. Percent decrease in coronary vascular resistance was greater and percent decrease in renal vascular resistance was smaller than that in total peripheral vascular resistance with both nisoldipine and nifedipine. Results indicate that nisoldipine and nifedipine produce marked coronary vasoldilation and the vasodilating effect of nisoldipine lasts longer than that of nifedipine.

Anesthesia↗
PubMed1986

Effects of the water extract of Chrysanthemum indicum Linn. on coronary and systemic hemodynamics in the dog.

To clarify the pharmacological profile and the mechanism of action of the water extract of flower of Chrysanthemum indicum Linn. (CIL), a crude drug, the effects of CIL on coronary and systemic hemodynamics were examined in anesthetized open-chest dogs, and the coronary relaxing action of CIL was tested on isolated dog coronary arterial strips. Intravenous administration of CIL 5-20 mg/kg produced a decrease in aortic blood pressure and increases in coronary blood flow, left ventricular dP/dt and heart rate in a dose-dependent manner. Renal blood flow initially decreased and then increased to the values above the preinjection level. These changes by every dose of CIL returned to the preadministration level until 5 min. Dipyridamole (0.1 mg/kg i.v.) potentiated an increase in coronary blood flow of CIL and aminophylline (1.0 mg/kg i.v.) attenuated this response. Intravenous administration of adenosine 5-50 micrograms/kg produced effects similar to those of CIL. The doses of CIL and adenosine which produced a two-fold increase in coronary blood flow were 13.8 mg/kg and 29.5 micrograms/kg, respectively. In 30 mM potassium-induced contracture of dog coronary arterial strips, there was no difference in the relaxant response to CIL between large coronary arteries and medium-size coronary arteries. Adenosine tended to produce a larger relaxation in medium-size coronary arteries than in large coronary arteries. The results indicate that CIL has a coronary vasodilating action and a renal vasoconstricting action in the open-chest dog and that the pharmacological profile of CIL is in part similar to that of adenosine.

Adenosine↗
PubMed1986

Effects of trapidil on diltiazem-induced changes of mechanical and electrical properties in isolated rabbit myocardium.

Effects of trapidil on diltiazem-induced changes of myocardial properties were investigated mechanically and electrophysiologically in tissues isolated from rabbit hearts. Application of diltiazem (10(-6) M) on right atria significantly decreased both force development and contraction rate. Additional administration of trapidil (10(-4) M) in the presence of diltiazem significantly restored the magnitude of force development without changes in contraction rate. Electrical stimulation to left atria and papillary muscles with varying frequencies produced a frequency-dependent increase in force developments (Bowditch's staircase). Diltiazem (10(-6) M) caused a depression of contractile force hence inhibited the staircase upon increasing frequency of stimulations. Additional application of trapidil (10(-4) M) partially but significantly restored the staircase. Intracellular recordings with microelectrodes clarified that trapidil increased the amplitude of slow responses which was being depressed by the treatment of diltiazem. Our findings suggest that trapidil, when applied successively to diltiazem, may diminish the inhibitory effects of diltiazem on hearts.

Animals↗
PubMed1985

Microsomal calcium-accumulating ability of bovine coronary artery and aorta.

Calcium uptake and binding activities of microsomal fractions from bovine coronary artery and aorta were examined. The isolated microsomal fraction of the coronary artery and aorta showed 7- to 8-fold higher glucose-6-phosphatase activity and 4- to 6-fold higher NADPH-cytochrome c reductase activity as compared with the corresponding values for the homogenate fraction. Coronary artery and aorta microsomal calcium uptake activities were 118 and 159 nmoles Ca2+/mg protein/10 min in the presence of 100 microM CaCl2, respectively. These activities for bovine vascular smooth muscle microsomes are higher than those of other species investigated. The calcium uptake activities were dependent on calcium concentrations ranging from 5 to 50 microM in the assay medium. The onset of the reaction for aorta microsomal calcium uptake was faster than that for the coronary artery. The calcium uptake activity was also dependent on ATP, but it was practically independent of oxalate ions in the assay medium. Microsomal calcium binding activities of the coronary artery and aorta were maximal at 20 min of incubation under the present experimental conditions. A lower Km value of the aortic calcium binding for ATP was obtained as compared with that for the coronary artery. The present experiment explored several characteristics of the microsomal calcium-accumulating ability of vascular smooth muscle, which provides meaningful information for further study on cellular calcium movements in vascular smooth muscle.

Adenosine Triphosphatases↗
PubMed1985

A possible action of nicardipine on the cardiac sarcolemmal Na+-Ca2+ exchange.

The effects of nicardipine on sodium-calcium exchange activity of cardiac sarcolemma-enriched vesicles isolated from the rat heart were examined. Sodium-loaded, sarcolemma-enriched vesicles, when exposed to a medium containing 40 microM CaCl2, exhibited about 5 nmoles Ca2+/mg protein of the maximal calcium uptake; the initial rate was 21 nmoles Ca2+/mg protein/min. The calcium uptake was dependent on the extravesicular concentration of calcium ion. Nicardipine at concentrations of 0.1 to 10 microM depressed the rate of calcium uptake activity by 60-90%. The isolated membrane vesicles preloaded with Ca2+ showed a calcium efflux activity, when exposed to a medium containing sodium ion. The rate of calcium efflux was 2.5 nmoles Ca2+/mg protein/min, when measured in a medium containing 6.5 mM NaCl. The efflux rate was facilitated with increased concentrations of sodium ion in the medium. About 75% of the preloaded calcium in the vesicles was released within 3 min of incubation. The rate of calcium efflux was stimulated in the presence of 0.1 to 10 microM nicardipine (2.5- to 4-fold increase). The present results suggest a possible action of nicardipine on the sodium-calcium exchange mechanism at cardiac sarcolemmal sites.

Adenosine Triphosphatases↗
PubMed1985

Effect of intracoronary captopril on coronary blood flow and regional myocardial function in dogs.

To evaluate the cardiac effect of an inhibitor of angiotensin-converting enzyme, the effect of intracoronary (i.c.) captopril on coronary blood flow and regional myocardial function was examined in the anesthetized open-chest dog. Blood flow of the left circumflex coronary artery (LCX), left ventricular pressure (LVP), aortic pressure (AoP) and regional myocardial segment length were measured continuously. Captopril i.v. (0.3 mg/kg) produced an immediate reduction in AoP and an increase in percent shortening of myocardial segments followed by a decrease in coronary vascular resistance and increases in heart rate and LVdP/dt. Reductions in LCX flow induced by i.c. angiotensin were attenuated and i.c. bradykinin-induced increases in LCX flow were augmented after captopril. On the contrary, i.c. infusion of captopril (0.01 mg/min) into the LCX caused no change in hemodynamic variables and myocardial shortening although responses to angiotensin I and bradykinin were markedly modified. These results suggest that captopril may have no direct cardiac effect.

Acetylcholine↗
PubMed1985

Comparison of the effects of primary prostaglandins on isolated human urinary bladder.

The effects of primary prostaglandins (PGs) on the dome and trigone of the human urinary bladder were investigated in vitro. In the dome preparations, PGE1 (10(-9) to 10(-6) gm./ml.) showed a weak contractile effect, while PGE2 (10(-9) to 10(-6) gm./ml.) produced dose-dependent contractions. PGF2 alpha (10(-9) to 10(-6) gm./ml.) induced contractions greater than those induced by PGE1 and PGE2. In the trigone preparations, PGE1 (10(-9) to 10(-6) gm./ml.) had no effect, and PGE2 (10(-9) to 10(-6) gm./ml.) produced only a weak contractile response. PGF2 alpha (10(-9) to 10(-6) gm./ml.) showed a greater contractile potency than PGE2. Contractile responses of both preparations to PGE1, PGE2 and PGF2 alpha were not affected by pretreatments of atropine, hexamethonium and phentolamine. These results suggest that the order of potency of primary PGs to induce contractile responses is PGF2 alpha greater than PGE2 greater than PGE1 in both the dome and the trigone preparations, and that the contractile effects of PGE1, PGE2 and PGF2 alpha may not be mediated by activation of muscarinic, nicotinic or adrenergic alpha-receptors.

Acetylcholine↗
PubMed1985

Characterization of membrane-bound adenosinetriphosphatase activity of sarcolemma-enriched fraction from vascular smooth muscle.

Membrane-bound adenosinetriphosphatase (ATPase) activities of the sarcolemma-enriched fraction from bovine aorta were characterized. The membranes, isolated by a sucrose density gradient method, were enriched about 31-fold in sodium- and potassium-stimulated, magnesium-dependent ATPase (Na,K-ATPase) activity, and about 8-fold in 5'-nucleotidase activity compared to the homogenate, suggesting that the isolated membranes were substantially enriched with the sarcolemma. The membranes exhibited about 31, 33 and 42 mumol Pi/mg protein/h of Na,K-ATPase, magnesium-dependent ATPase and calcium-dependent ATPase activities, respectively, in the presence of 4 mmol/l ATP. The sarcolemma-enriched membranes required considerably high concentrations of well-known inhibitors for Na,K-ATPase such as vanadate (more than 1 mumol/l), lanthanum (more than 1 mmol/l) and calcium (10 mmol/l), to induce a significant inhibition in the Na,K-ATPase activity. Treatments of the membrane with physical disruptions and sodium dodecyl sulfate or deoxycholate reduced the total Na,K-ATPase activity, and did not expose fully the ouabain sensitivity of the Na,K-ATPase. These results indicate that there are marked differences in the properties of the ATPase between vascular smooth muscle sarcolemma and cardiac sarcolemma.

Adenosine Triphosphatases↗
PubMed1985

Heat stable protein with anticoagulant and smooth muscle contractile actions isolated from Habu (Trimeresurus flavoviridis) venom.

The biological activity of a Habu (Trimeresurus flavoiridis) venom fraction with drug-metabolizing enzyme inhibitory action was studied. The venom fraction, which was isolated through Sephadex G-100 gel filtration and cation exchange chromatography on Amberlite CG50, caused an increase of vascular permeability and hemorrhage, but these actions were lost after heating at 70 degrees C for 5 min. The fraction showed anticoagulant activity on citrated blood, and this activity remained after heating of the venom. Guinea pig ileum was contracted by treatment with nonheated or heated venom fraction, and these contractions were inhibited with atropine and potentiated with physostigmine. These results suggest that the drug-metabolizing enzyme inhibitor isolated from Habu venom involves the heat stable component with anticoagulant activity and smooth muscle contractile action.

Animals↗
PubMed1985

Calcium accumulating ability of mitochondria from bovine coronary artery. Comparison with aortic mitochondria.

The calcium accumulating ability of mitochondria isolated both from bovine coronary artery and aorta was investigated. Coronary artery and aorta were pretreated with 0.1% collagenase. Cytochrome c oxidase activities of mitochondria isolated from coronary artery and aorta showed 25-fold and 19-fold increases, respectively, as compared with those of each homogenate, whereas NADPH-cytochrome c reductase, potassium-phosphatase and Na+-K+ ATPase activities increased less than 2-fold. This suggests that the isolation procedure is capable of obtaining a subcellular fraction highly enriched with mitochondria. Mitochondrial calcium uptake activity of the coronary artery was approximately 250 nmoles Ca2+/mg protein/10 min, and was markedly depressed with metabolic inhibitors such as NaN3, ruthenium red and 2,4-dinitrophenol. Calcium uptake activity of bovine aortic mitochondria showed similar activity and a similar trend in sensitivity to metabolic inhibitors. By contrast, the onset of the calcium binding reaction of the aortic mitochondria was slower and the azide-sensitivity of the mitochondria to magnesium ATPase activity was lower than those for coronary artery mitochondria. The present study has provided a method for isolation of mitochondria with a high capacity of calcium uptake activity, which may prove meaningful for future physiological and pharmacological evaluation of mitochondrial calcium accumulation in vascular smooth muscle.

Alkaline Phosphatase↗
PubMed1985

Effects of nipradilol (K-351) on cardiac function in anesthetized open-chest dogs.

Effects of nipradilol (K-351) on cardiac performance and myocardial oxygen consumption were investigated in anesthetized open-chest dogs. Nipradilol 0.1 mg/kg i.v. induced falls in systolic and diastolic aortic blood pressure and left ventricular pressure, and decreases in cardiac output, coronary sinus outflow, left ventricular dP/dt and heart rate. Stroke volume was transiently increased and left ventricular stroke work index was significantly decreased, while left ventricular mechanical efficiency was not significantly changed. Myocardial oxygen consumption was significantly decreased. Total peripheral vascular resistance and coronary vascular resistance were persistently increased. Left ventricular enddiastolic pressure was not significantly changed. These results suggest that nipradilol has a possible antianginal property through a decrease in myocardial oxygen consumption due to a fall in aortic blood pressure and a decrease in heart rate.

Adrenergic alpha-Antagonists↗
PubMed1985

Effect of nifedipine treatment on cardiac myosin ATPase activity and responsiveness of cardiovascular system in the dog.

Effects of nifedipine treatment on cardiac myosin ATPase activity and responsiveness of cardiovascular system to catecholamine have been studied. Eight mongrel dogs weighing 7.5 to 13.5 kg were given nifedipine orally twice daily (60 mg/day) for 2 weeks. Ten minutes after the first administration of nifedipine (30 mg p.o.) the heart rate increased significantly and it lasted for, at least, 4 hours. Two-week treatment of nifedipine caused a decrease of the resting heart rate, but the maximal heart rate increase by nifedipine administration was almost the same as the one on the first day. The effects of norepinephrine on heart rate and blood pressure, responsiveness of isolated coronary arteries to some agents inducing a contraction and, Ca2+-activated and K+-activated cardiac myosin ATPase activities were not significantly different between control and nifedipine treatment groups.

Adenosine Triphosphatases↗
PubMed1985

Comparison of the effects of nifedipine on ureter and coronary artery isolated from the dog.

The effect of nifedipine (Adalat) on isolated dog ureter was compared with that on isolated coronary artery. Nifedipine at a concentration of 10(-8) mol/l significantly decreased the frequency of ureteral rhythmic contractions evoked by potassium, and suppressed the force of these contractions at a concentration of 3 X 10(-8) mol/l. In potassium-contracted coronary artery strips, nifedipine at concentrations more than 3 X 10(-9) mol/l produced significant relaxations in a concentration-dependent manner. The results indicate that nifedipine is able to act inhibitorily on ureteral contractions, and inhibition of pace making activities in ureteral smooth muscle was suggested as a mode of action of nifedipine.

Animals↗
PubMed1985

Effects of diltiazem on the TEA-induced plateau of nodose ganglion action potentials.

The effects of diltiazem, a Ca2+-antagonist, on the tetraethylammonium (TEA)-induced plateau of the action potentials of nodose ganglia in the rabbit were investigated with intracellular recording techniques. TEA (10mM) formed a long lasting plateau in the falling phase of action potentials when applied in the superfusion solution. Membrane conductance during the plateau was increased and both duration and amplitude of the plateau were Ca2+-dependent. Hyperpolarizing test pulses terminated this TEA-induced plateau whereas depolarizing pulses prolonged it. Diltiazem depressed this TEA-induced plateau dose-dependently (I50 value, 8.6 X 10(-7) M). The present results provide evidence that plateau is elicited by the activation of a voltage-dependent Ca2+-influx and suggest that the TEA-induced plateau could be a useful tool to investigate the inward Ca2+-current in the neuron.

Action Potentials↗
PubMed1984

Possible alpha-adrenoceptor blocking activity of arotinolol (S-596), a new beta-adrenoceptor blocking agent in isolated dog coronary artery.

Effects of arotinolol on dog coronary arteries were investigated in vitro. In distal portions of left circumflex coronary arteries contracted with 3 X 10(-2)M KCl, norephinephrine relaxed the strips in a concentration-dependent fashion. Propranolol (10(-6)M) converted the norepinephrine-induced relaxations to contractions, and arotinolol (10(-6)-10(-5)M) inhibited the relaxations induced by norepinephrine in a concentration-dependent manner. In proximal portions of the strips after potassium-contracture, norephinephrine produced concentration-dependent contractions which were augmented by propranolol (10(-6)M) and inhibited by arotinolol (10(-6)-10(-5)M). These results suggest that arotinolol has an alpha-adrenoceptor blocking activity in addition to a beta-adrenoceptor blocking action in dog coronary arteries.

Adrenergic alpha-Antagonists↗
PubMed1984

Effects of an antihypertensive agent, nipradilol, on isolated coronary artery of the dog.

Effects of nipradilol on proximal, middle and distal portions of left coronary arteries of the dog were investigated in vitro. Nipradilol (10(-7)-10(-3) M) produced a concentration-dependent relaxation in helical strips of isolated coronary artery under potassium contracture. The relaxation in the middle portions was most pronounced, it was 10% of the equimolar concentrations of nitroglycerin and significantly greater than that of propranolol. In the proximal portions of the coronary arteries, nipradilol (3 X 10(-8)-3 X 10(-7) M) showed a tendency to augment the contractile responses to norepinephrine; in the middle portions it reversed the relaxant responses to norepinephrine into contractile effects in a concentration-dependent manner. In distal portions, nipradilol significantly decreased the relaxant responses of the strips to norepinephrine. The findings demonstrate direct vasodilating and beta-adrenoceptor blocking actions of nipradilol in isolated coronary arteries of the dog.

Adrenergic beta-Antagonists↗
PubMed1984

Actions of some autonomic drugs on spontaneous contractions of isolated dog ureter.

Effects of some autonomic drugs on the isolated dog ureteral preparations showing spontaneous contractions were investigated quantitatively. Noradrenaline, adrenaline and phenylephrine produced increases in frequency and tension of the contractions which were reversed to decreases or depressed by phentolamine. Isoproterenol abolished the spontaneous contractions. Acetylcholine did not significantly change frequency and tension of the contractions. The results indicate that ureteral spontaneous contractions may be enhanced through an activation of alpha-adrenoceptors and be attenuated through an activation of beta-adrenoceptors. However, acetylcholine will not display an important role on the ureteral contractions.

Animals↗