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Biomedical subjects

M Sakanashi

Publications and source records attributed to M Sakanashi.

At least 127 records · Page 7Linked to original sources

A further study on constrictor responses of dog coronary arterial strips to acetylcholine under potassium-contracture.

Experiments were designed to clarify what mechanisms are involved in the contraction of dog coronary artery induced by acetylcholine. Helical strips cut from the left circumflex coronary artery were suspended in a bath filled with oxygenated Krebs-Ringer solution at 37 degrees C, and tension developments were recorded isometrically. During potassium-contracture acetylcholine produced further contractions of the strips, which were significantly depressed by atropine together with phentolamine or atropine together with d-tubocurarine. In the strips prepared from dogs in which 6-hydroxydopamine was administered 2 hrs before isolation of hearts, acetylcholine-induced contraction was suppressed by atropine alone. Norepinephrine produced contractions in these strips, which were blocked by phentolamine. Results indicate that acetylcholine may directly constrict the artery through a muscarinic action and simultaneously produce norepinephrine release from sympathetic nerve endings by acting on presynaptic nicotinic receptors resulting in the contraction of the artery.

Acetylcholine↗

Depressant effect of trapidil on dog coronary arterial contraction induced by ergonovine.

Effects of trapidil on ergonovine-induced contractions of isolated dog coronary arteries were investigated in vitro. Ergonovine produced dose-dependent contractions of helical strips cut from the left circumflex branches of coronary arteries. Trapidil significantly depressed these-contractions. 5-HT also produced dose-dependent contractions of the strips, which were depressed by trapidil. In isolated rabbit femoral arterial preparations, norepinephrine dose-dependently contracted the strips. Phentolamine significantly depressed these contractions, and trapidil depressed them when relatively high doses were applied previously. Results indicate that trapidil has a depressant effect on coronary arterial contractions induced by ergonovine, partly through antagonism to 5-HT receptor and/or adrenergic alpha receptor.

Animals↗

Participation of coronary perfusion pressure in transmural energy metabolism in the hypoperfused canine heart.

The participation of coronary perfusion pressure in hemodynamic and transmural metabolic changes was examined in the open chest canine heart. At lower pressure than 50% of the control, reactive hyperemia disappeared and the coronary arterial inflow precipitously decreased. In 8 dogs, when the coronary arterial inflow was decreased to 47-49% of the control by coronary constriction for 15 min, the coronary perfusion pressure fell in various degrees ranging from 39 to 73% of the control. At a lower pressure than 60% of the control, creatine phosphate (CP) content and its ratio of subendocardium (ENDO) to subepicardium (EPI) decreased, while lactate (LA) content and its ratio of ENDO to EPI increased depending on the degree of the fall in coronary perfusion pressure. A little decrease in ATP content was produced only in the subendocardium under the lower pressure than 50% of the control. When the CP content decreased to below one-third of the control, the significant accumulation of lactate and the precipitous decrease in ATP occurred. Our results suggest that the coronary perfusion pressure has an important role for a severity of the transmural energy metabolism in the hypoperfused ventricle.

Animals↗

Effect of trapidil on mechanical and electrical activity of isolated rabbit atrium.

Actions of trapidil on mechanical and electrical activities of rabbit right atria were investigated in vitro. Isolated atria had spontaneous contractions. Ca++ (2.7-4.5 mM) concentration-dependently increased force and frequency of atrial contractions, and trapidil (10(-5)-10(-4) g/ml) also did. Trapidil (10(-5)-10(-4) g/ml) showed a tendency to augment the positive inotropic action of Ca++ and significantly enhanced the positive chronotropic action of Ca++. In experiments using conventional microelectrode techniques, trapidil (10(-5)-10(-4) g/ml) concentration-dependently increased the slope of slow diastolic depolarization, the maximal diastolic potentials and the peak potentials in pacemaker potentials of sinoatrial nodal cells, and shortened the cycle length of them. The results indicate pharmacodynamically and electrophysiologically that trapidil produces a positive inotropic and chronotropic effect on isolated rabbit right atria.

Animals↗

A study on constrictor response of dog coronary arteries to acetylsalicylic acid.

The present study was designed to investigate the effects of acetylsalicylic acid at a high dose on dog coronary arteries. In the isolated and perfused dog hearts, an intracoronary injection of acetylsalicylic acid (10 mg) decreased coronary blood flow concomitant with diminution of myocardial contractile force, but did not change heart rate. In the isolated dog coronary arterial strips, acetylsalicylic acid (10-4 M) produced the contractions of them, which were significantly inhibited by calcium-free solution, diltiazem, nifedipine, phospholipase A2, arachidonate and prostaglandin E1. The results indicate that acetylsalicylic acid at a high dose produces coronary arterial contracture probably through inhibition of intravascular synthesis of vasodilating prostaglandins.

Animals↗

Changes in vascular reactivity in rats with experimental renal insufficiency.

In ureter-ligated rats, the pressor effects of both norepinephrine and angiotensin II i.v. on systemic blood pressure and serum sodium concentration were significantly decreased when compared with those in control rats, while serum potassium concentration, blood urea nitrogen, mean systemic blood pressure and plasma renin activity were significantly increased. The microscopic examination of aortic smooth muscles did not show significant histological lesions in the tissues obtained from ureter-ligated rat. The responsiveness of aortic strips isolated from ureter-ligated rats to norepinephrine and angiotensin II was significantly decreased in comparison with that from control rats. The results suggest that a decreased pressor response to norepinephrine and angiotensin II under ureter-ligated conditions may be attributed to a decrease in vascular reactivity to drugs.

Angiotensin II↗

On the mode of action of ergometrine in the isolated dog coronary artery.

Coronary vasoconstrictor responses to ergometrine were examined in spiral coronary arterial preparations of dogs. Either ergometrine or serotonin (5-HT) produced dose-dependent contractions of the strips. Methysergide significantly depressed the contractions induced by ergometrine or 5-Ht. Dihydroergotamine and phentolamine depressed constrictor responses to ergometrine, while phenoxybenzamine did not. The 5-HT antagonistic action of phentolamine was stronger than that of phenoxybenzamine. The results indicate that ergometrine may act on coronary arteries mainly through activation of 5-HT receptors.

Animals↗

Analysis of relaxant effects of trapidil in isolated dog coronary artery.

Effects of 7-diethylamino-5-methyl-s-triazolo [1,5-a]pyrimidine (trapidil, Rocornal) on dog coronary arteries were investigated in vitro. Trapidil produced dose-dependent relaxations of isolated arteries which were contracted with potassium or prostaglandins F2 alpha. These effects of trapidil were not affected by atropine and propranolol. 5-Hydroxytryptamine (5-HT) and phenylephrine dose-dependently increased the tension of isolated coronary arteries. Trapidil could inhibit these effects of 5-HT or phenylephrine. The results indicate that trapidil has not a muscarinic action and an adrenergic beta-receptor stimulating action, but it has a 5-HT receptor and an adrenergic alpha-receptor blocking action.

Acetylcholine↗

Effects of prostaglandin E1 on isolated dog renal artery.

Actions of prostaglandin (PG) E1 were investigated using isolated dog renal arterial strips. Norepinephrine increased the tension of the renal arterial strips contracted with potassium, and this response was depressed by phentolamine. Isoproterenol produced relaxant effects on these arteries, and this response was converted to contractile one by propranolol. Diltiazem dose dependently relaxed the potassium-contracted strips. PGE1 (10(-9)-3 X 10(-8) Gm./ml.) constricted the renal arterial strips, while in higher concentrations (10(-7)-3 x 10(-7) Gm./ml.) it caused relaxations of them. Contractile responses by PGE1 were not affected by phentolamine or phenoxybenzamine, but were suppressed by diltiazem. On the other hand, relaxant effects of PGE1 were not changed by propranolol. Papaverine or theophylline significantly inhibited the contractions induced by PGE1. From these results it is suggested that (1) in the dog renal artery adrenergic alpha-receptors must be more dominant than beta-receptors; (2) PGE1 will produce a depolarization of renal arterial smooth muscle and/or increase an active transport of calcium ions into smooth muscle cells; and (3) the relaxant responses by PGE1 may be related to an increase in cellular cyclic adenosine monophosphate (AMP) contents.

Animals↗

Effects of vasodilators on microcirculation of the rat cremaster muscle: a microscopic method for screening drugs.

Effects of vasodilating drugs on microcirculation of the rat cremaster muscle were investigated microscopically. Topical application and intravenous injection of papaverine produced dilatation of arterioles. Cyclandelate applied topically dilated the arterioles to a considerable extent. Topical application of bamethan induced arteriolar dilatation while bamethan given intravenously constricted the arterioles. Kallikrein applied topically induced a slight dilatation of arterioles, and intravenous administration of kallikrein produced an appreciable vasodilatation. Topical administration of bradykinin produced a vasodilatation of arterioles of the rat cremaster muscle. These results indicate that direct action of a drug on the microcirculation can be properly evaluated by the microscopic method in the rat cremater muscle, if the drug is applied topically, in the vicinity of small vessels under study.

Acetylcholine↗

Responsiveness and high-energy phosphate metabolism of isolated dog coronary arteries.

The relationship between responsiveness and high-energy phosphate metabolism was observed in isolated dog coronary arterial strips before and after equilibration, under aerobic conditions. The strips responded slowly to potassium, norepinephrine, isoproterenol and 5-hydroxytryptamine before being equilibrated but did respond quickly to these drugs after being equilibrated for 1 hour under aerobic conditions. The contents of ATP, creatine phosphate (CP) and lactate were not significantly altered before and after equilibration for 1 hr. It is proposed that, before being equilibrated under aerobic conditions, coronary arteries may be unable to utilize ATP and CP due to injury of contractile or relaxant mechanisms resulting in a weak vascular responsiveness.

Adenosine Triphosphate↗

Effects of 2-nicotinamidoethyl nitrate (SG-75) on dog coronary artery and cat papillary muscle.

Effects of 2-nicotinamidoethyl nitrate (SG-75) on isolated dog coronary artery and cat papillary muscle were investigated. SG-75 dose-dependently relaxed the isolated coronary arterial strips contracted with potassium. Large doses of SG-75 depressed contraction of papillary muscle driven with electrical stimulation and inhibited enhancement of contraction of papillary muscle induced by calcium and isoproterenol. From these results it is suggested that SG-75 may have a weak Ca++-antagonistic action.

Animals↗

Inhibition of constrictor responses of dog coronary artery by atropine. A possible effectiveness of atropine on variant form of angina pectoris.

A possible effectiveness of atropine on variant form of angina pectoris was investigated using the left circumflex coronary arterial strips of dogs. Acetylcholine 10(-5)--10(-3) Gm/ml dose-dependently constricted the isolated arterial strips during potassium-contracture in 6 cases, and repetitive applications of acetylcholine could produce the similar contractions to the control. In 18 strips atropine 10(-6) Gm/ml significantly depressed the contractions of coronary arteries induced by acetylcholine 10(-5)--10(-3) Gm/ml. In 5 arterial strips atropine 10(-6) Gm/ml significantly inhibited norepinephrine-induced responses of these arteries, and by 10(-5) Gm/ml further suppression of the responses was obtained. The results suggest that atropine may suppress the contractile responses of the coronary artery induce by acetylcholine and nonrepinephrine through a muscarinic-receptor blocking action and simultaneously partly through an adrenergic alpha-receptor blocking action.

Acetylcholine↗

Analysis of vasodilatory action of a new nitroester agent, 2-nicotinamidoethyl nitrate (SG-75).

Effects of 2-nicotinamidoethyl nitrate (SG-75) on cardiovascular system were investigated using whole animals and isolated vascular smooth muscles of dogs and rabbits. In dogs in vivo SG-75 i.v. produced dose-dependent falls in systemic blood pressure (SBP) concomitant with increases in heart rate (HR). Hypotension by SG-75 was not affected by propranolol and atropine but slightly inhibited by diphenhydramine. Norepinephrine (NE) dose-dependently increased SBP, and SG-75 could not affect these effects of NE. In dog coronary arterial strips contracted with potassium, SG-75 produced a dose-dependent relaxation of these strips. These effects of SG-75 were not affected by propranolol and atropine, but slightly inhibited by diphenhydramine. NE dose-dependently increased the tension of helical strips prepared from rabbit femoral artery, rabbit aorta and dog coronary artery. But SG-75 could not alter these effects of NE. The results suggest that SG-75 may have not an adrenergic beta-receptor stimulating action, a muscarinic action and an adrenergic alpha-receptor blocking action, but an inconsiderable histamine-like action. Probably, a main action of SG-75 may be a nitroglycerin-like action.

Animals↗

Effects of theo-esberiven on the development of collateral circulation in dog hearts.

Effects of Theo-Esberiven, a coronary vasodilator, on the development of collateral circulation were investigated in dogs with their left anterior descending artery chronically occluded. The drug was administered i.v. at 0.1 ml/kg once a day for 1 to 4 weeks after the occlusion. Left circumflex coronary flow in dogs treated with the drug was increased over the value in control ones when measured one week after the occlusion. At the same time, the ratio of retrograde pressure to perfusion pressure, which correlates negatively with the collateral vascular resistance, significantly exceeded the value in control (P less than 0.05). On the basis of observations with blood vessel casts of hearts, distinct anastomoses between the circumflex and anterior descending arteries had already been observed in all preparations from dogs treated for 2 weeks in contrast to the findings seen in control ones. There were less histological changes in myocardial tissue obtained from dogs treated for one week than those in control ones. From these results, Theo-Esberiven appears possibly to accerelate the collateral development at the earlier stages after the coronary occlusion.

Aminophylline↗

High-energy phosphate metabolism of isolated coronary arteries in the dog.

The correlation between phosphate metabolism and isometric contraction was investigated in helical strips from dog coronary artery. Adenosine triphosphate (ATP) and creatine phosphate (CP) contents of resting strips did not significantly change during anoxia. ATP content remained unchanged during potassium-contracture under aerobic conditions but was significantly reduced by anoxia. Pretreatment with iodoacetate resulted in a striking reduction in ATP content with a less marked decrease in CP content. ATP-depleting effect of iodoacetate was reduced slightly by the addition of pyruvate, but contractile response was not restored. It is considered that high-energy phosphates provided by anaerobic glycolysis can meet the energy requirements of resting coronary vessels but are insufficient for maintaining active tension. In resting strips equilibrated for 2 h in oxygenated bath solution, the reactivity to KCl and anoxia appears to be dependent on the availability of ATP.

Adenosine Triphosphate↗

[Effects of Theo-Esberiven on the coronary circulation and myocardial metabolisms in dogs (author's transl)].

In isolated dog heart, Theo-Esberiven 0.1 mg, which contains 12 mg proxyphylline, 2.5 mg rutin and 5 mg Melilotus extract, and proxyphylline (12 mg) increased coronary blood flow (CBF) and was associated with increased heart rate (HR) and myocardial contractile force (MCF). The effect of Theo-Esberiven on CBF was about 1.7 times higher than that of proxyphylline. Theo-Esberiven did not significantly affect myocardial oxygen consumption (QO2) and redox potential (deltaEh), while proxyphylline aggravated myocardial metabolisms, as determined from these parameters. Esberiven 0.1 ml, which contains 2.5 mg rutin and 5 mg Melilotus extract, slightly but signficantly increased CBF and decreased QO2 and deltaEh without changing HR and MCF. In situ, intra-coronary injection of either Theo-Esberiven or proxyphylline resulted in a dose-dependent increase in left circumflex coronary flow (LCCF). The effect of Esberiven on LCCF was much less and was slight at the higher doses. Intravenous injection of Theo-Esberiven (0.1 ml/kg) increased LCCF. Besides this change, marked fall in blood pressure and tachycardia were induced by both Theo-Esberiven and proxyphylline without the change in dP/dtmax. Esberiven by the same route led to the decrease in blood pressure associated with HR and dP/dtmax. These results indicate that Theo-Esberiven may be appropriately prescribed for ischemic heart diseases.

Action Potentials↗