Search PubMed⌕ Search

Biomedical subjects

J Aono

Publications and source records attributed to J Aono.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of bunitrolol on adrenergic and serotonergic receptors.

To assess the importance of anti-adrenergic and anti-serotonergic activities of bunitrolol for its efficacy as an antihypertensive and antianginal agent, effects of this substance on the binding of adrenergic and serotonergic agents to the respective receptors of the rat brain, rat heart, dog brain, and/or dog aorta were examined using the radioligand binding assay methods. In addition, the pA2 values of bunitrolol as an antagonist against the positive chronotropic and inotropic actions (beta 1-adrenoceptor) of isoproterenol were also determined by pharmacological methods using the isolated guinea pig atria. To assess the specificity, pA2 values were also obtained in the isolated trachea (beta 2-adrenoceptor) using isoproterenol as an agonist and in the isolated aorta from the guinea pig and the rat using phenylephrine as an agonist (alpha 1-adrenoceptor). A strong inhibition by bunitrolol of 3H-dihydroalprenolol (3H-DHA) binding to beta-adrenoceptors was observed, while the inhibition of 3H-prazosin binding to alpha 1-adrenoceptors, 3H-serotonin binding to 5HT1-receptors. 3H-p-aminoclonidine binding to alpha 2-adrenoceptors, and 3H-ketanserin binding to 5HT2-receptors were found to be very weak. The rank order of antagonistic potencies of bunitrolol against the adrenergic receptors as assessed with pA2 values were beta 1 greater than beta 2 much greater than alpha 1. From these two different types of experiments, it is clear that the antihypertensive and antianginal effects of bunitrolol are mainly due to its beta-blocking actions, with the alpha 1-blocking action of this drug playing a minor role.

Animals↗
PubMed1987

MC-838 (altiopril calcium): a novel orally active angiotensin converting enzyme inhibitor.

MC-838, calcium (-)-N-[(S)-3-(N-cyclohexylcarbonyl-D-alanyl) thio]-2-methylpropionyl]-L- prolinate, is a new orally active angiotensin converting enzyme (ACE) inhibitor in which the mercapto-group is taken up in a stable thiolester linkage. The linkage was relatively resistant against enzymatic hydrolysis by rat liver homogenates. The ACE prepared from rabbit lung was inhibited by MC-838 in a concentration-dependent manner. In isolated rat aortic ring and guinea-pig ileum preparations, MC-838 was highly specific in suppressing the contractile response to angiotensin-I (A-I) an in augmenting the contractile one to bradykinin. However, the ACE inhibitory activity of MC-838 was 30-100 times less potent than that of captopril. In conscious two-kidney (2 KG), renal hypertensive rats and spontaneously hypertensive rats (SHRs), MC-838 (3 and 10 mg/kg) given orally caused a long-lasting hypotensive effect with a slow onset. When compared on a weight basis (3 mg/kg), the antihypertensive effect of MC-838 was comparable to that of captopril in magnitude, but the duration of action of MC-838 was approximately 2 times longer than that of captopril.

Administration, Oral↗
PubMed1986

Effects of a new antihypertensive agent, SGB-1534, on rat platelet aggregation.

The present study was designed to examine the antiplatelet activity of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4(1H, 3H)- quinazolinedione monohydrochloride, compared with prazosin, ketanserin and aspirin. The equihypotensive doses of SGB-1534, prazosin and ketanserin were administered orally to rats; and 1 hr later, their effects on collagen-induced platelet aggregation, compared with those of aspirin, were examined under ex vivo conditions. The bleeding time was determined by using the tail transection method. SGB-1534 (10 mg/kg) as well as ketanserin (3 and 10 mg/kg) and aspirin (10 mg/kg) effectively inhibited the platelet aggregation; and in addition, they significantly prolonged bleeding times. Prazosin in doses of 10 and 30 mg/kg did not affect either the aggregation or bleeding times. Whereas 10(-4) M aspirin significantly inhibited the production of malondialdehyde (MDA) in rat platelets, SGB-1534, prazosin and ketanserin even in considerably high concentrations (10(-4) or 10(-3) M) did not affect the MDA production and the cyclic AMP levels in the platelets. In isolated rat femoral arteries, SGB-1534, prazosin and ketanserin antagonized the contractile response to phenylephrine with pA2 values of approximately 10.06, 10.39 and 7.71, respectively. Also, SGB-1534 and ketanserin attenuated the contractile response to 5-hydroxytryptamine (5-HT) with pA2 values of 6.36 and 9.53, respectively, while prazosin had no antagonistic effects on 5-HT-induced contraction.

Adrenergic alpha-Antagonists↗
PubMed1986

Effects of a new anti-inflammatory imidazole derivative, fenflumizole, on platelet aggregation in the rabbit.

The antiplatelet effect of fenflumizole, compared with aspirin or ticlopidine, was examined in in vitro, ex vivo and in vivo situations of the rabbit. Unlike ticlopidine, fenflumizole and aspirin effectively inhibited in vitro the platelet aggregation elicited by arachidonate and collagen. The activity of fenflumizole was 350 times more potent than that of aspirin. Fenflumizole (0.3-3 mg/kg) given p.o. was 4.2 and 8.1 times more potent than aspirin in inhibiting arachidonate- and collagen-induced platelet aggregations, respectively. Ticlopidine (300 mg/kg, p.o.) resulted in only weak effects on the aggregations. Fenflumizole (3 mg/kg) as well as aspirin (10 mg/kg) given p.o., unlike ticlopidine (300 mg/kg), effectively prevented the arachidonate-induced sudden death.

Animals↗
PubMed1985

Mechanism of the hypotensive effect of a novel phenylpiperazine derivative, SGB-1534: antagonism at alpha 1-adrenergic and 5-HT2 receptors.

The present in vivo and in vitro experiment was designed to examine the hypotensive mechanisms of 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4 (1H,3H)-quinazolinedione monohydrochloride (SGB-1534). The compound given orally significantly inhibited the pressor response to i.v. noradrenaline in rats and to 5-hydroxytryptamine (5-HT) in guinea-pigs but failed to block the pressor response to i.v. angiotensin II in rats. In pithed rats, SGB-1534 given i.v. had no effects on the prazosin-resistant part of the pressor effect of i.v. adrenaline, whereas it significantly inhibited the yohimbine-resistant part. In isolated guinea-pig aortae, SGB-1534 competitively inhibited the contractile response to noradrenaline with a pA2 value of 8.86, 6 times higher than prazosin. A combination of SGB-1534 with prazosin antagonized the noradrenaline effect as expected for a single class (alpha 1) of receptor. In isolated rabbit femoral arteries, SGB-1534 attenuated the contractile response to 5-HT with a pA2 value of 6.13, 400 times lower than ketanserin. A combination of SGB-1534 with ketanserin antagonized the 5-HT effect as expected for a single class (5-HT2) of receptor. In rat stomach fundus strips, SGB-1534 as well as ketanserin, even in a large dose, unlike methysergide, caused only slight inhibition of contractile response to 5-HT. These results indicate that SGB-1534 is a selective, competitive antagonist of the alpha 1-adrenoceptor and the 5-HT2 receptor, which may help to explain its antihypertensive properties.

Adrenergic alpha-Antagonists↗
PubMed1985

Antihypertensive effects of a novel phenylpiperazine derivative, SGB-1534, on several hypertensive models of rats.

The antihypertensive activities of SGB-1534, 3-[2-[4-(o-methoxyphenyl)-1-piperazinyl]ethyl]-2,4 (1H,3H)-quinazolinedione monohydrochloride, compared with prazosin, were examined in anesthetized or conscious hypertensive rat models. In anesthetized rats, SGB-1534 administered orally (3-10 mg/kg) reduced the blood pressure and significantly inhibited the pressor response to noradrenaline, but did not affect blood pressure responses to angiotensin II, isoproterenol, histamine and acetylcholine. This compound (0.1-3 mg/kg, p.o.) exhibited potent and long-lasting antihypertensive effects in conscious spontaneously hypertensive rats (SHRs), renal hypertensive rats and DOCA-salt rats, but it increased the heart rate only minimally. Repeated p.o. doses of SGB-1534 also reduced the blood pressure in SHRs without noticeable sign of tolerance to antihypertensive effects. In an experimental model for determining blood pressure compensation for postural tilt in anesthetized rats, SGB-1534 was free of postural effects, while prazosin induced orthostatic hypotension. In renal hypertensive rats and SHRs, SGB-1534, unlike prazosin, caused no increase in plasma renin activity. The present results reveal some pharmacological characteristics of SGB-1534 as an orally effective antihypertensive agent.

Animals↗
PubMed1984

Experimental myocardial infarction: effects of a lipid peroxide, 13-hydroperoxy linoleic acid on coronary circulation in rats.

Effects of 13-hydroperoxy linoleic acid on coronary circulation and vasculature were investigated using an electrocardiographic (ECG) and scanning electron microscopic (SEM) techniques. After the intra left ventricular injection of 13-hydroperoxy linoleic acid to rats the ischemic ECG changes, i.e., elevations of the ST segment and T wave, were observed with the reduction of systemic blood pressure and heart rate. By the SEM examination, the endothelial injuries were found with the platelet aggregation in the blood flow and the adherence of leukocytes. Thus it was clearly found that 13-hydroperoxy linoleic acid caused the various endothelial injuries and thrombus formation leading to coronary arterial occlusion. These results suggest that lipid peroxide may play an important role in the pathogenesis of vascular diseases especially in coronary vascular bed and take part in the generation of the severe myocardial ischemia.

Animals↗
PubMed1983

New 434-specific DNA binding protein copurified with the 434 tof protein from lambda imm434cI dv carrier cells of Escherichia coli.

A tof-like protein that has 434-specific DNA binding activity has been copurified with the 434 tof protein from lambda imm434cI dv carrier cells. The apparent molecular weight of the new 434-specific DNA binding protein is 9,000 to 9,500, a little higher than that of the 434 tof protein, as estimated by SDS gel electrophoresis. Amino acid analysis revealed the protein to be an arginine-rich component whereas the 434 tof protein is a lysine-rich component. The specific binding reaction of the new protein to lambda imm434dv DNA is distinct from that of the 434 tof protein in respect to the sigmoid shape of the binding curve and to the temperature dependency. This suggests that the specific binding to lambda imm434dv DNA observed with the new protein is due not to a trace of the 434 tof protein contaminating the new protein preparation but rather to the new protein itself. The NH2-terminal 11 residues of the new 434-specific DNA binding protein were sequenced by manual Edman degradation. This technique revealed that the new protein is not a fragment of the 434 tof, cII, or O protein or an NH2-terminal fragment of the cI repressor. The origin and the physiological roles of the new 434-specific DNA binding protein remain unknown.

Amino Acids↗
PubMed1982

Coliphage 434 tof Protein: NH2-terminal amino acid sequence and kinetic and equilibrium measurements of DNA binding.

Coliphage 434 tof protein was purified to a substantially pure state from lambda imm434 cI dv carrier cells. The minimum molecular weight is 7,500 +/- 500 as estimated by polyacrylamide gel electrophoresis. The amino acid sequence of the nine NH2-terminal residues was determined, by manual Edman degradation of the intact protein, to be Met-Gln-Thr-Leu-Ser-Glu-Arg-Leu-(Lys)-. The purified protein at low concentrations binds specifically to lambda imm434 dv DNA and at high concentrations also binds to lambda imm21 dv and lambda dv DNA. The curve of the specific binding is of Michaelis type, while that of the nonspecific binding is sigmoidal. The specific binding does not show marked temperature dependency at 4 degrees - 37 degrees C. We have analyzed the equilibrium and kinetic data of specific binding. The equilibrium dissociation constant is 1.9 X 10(-11) M at O degree C. The association rate constant and the dissociation rate constant are 1.1-2.9 X 10(8) M-1s-1 and 2.7 X 10(-3)s-1, respectively, at 0 degrees C. The half life of the tof protein-operator DNA complex is 260 s. These results suggest that the tof protein-operator interaction is much weaker than the interaction between the cI repressor and the operator reported by other workers.

Amino Acid Sequence↗
PubMed1981

Effects of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) on methacholine-induced ECG changes in intact anesthetized rats.

The effects of a newly developed nicotinamide derivative, N-(2-hydroxyethyl)nicotinamide nitrate (SG-75, Nicorandil), were examined in an experimental model of angina pectoris, utilizing methacholine-induced ECG changes as main parameter in intact anesthetized rats. The right carotid artery was exposed and through it a special cannula was inserted to a point near the right and left coronary ostium. Such a device made it possible to inject drugs more selectively into the coronary artery. Single intra-aortic injections of 4 to 8 micrograms of methacholine caused a transient elevation of the ST segment and T wave of the electrocardiogram (ECG). SG-75 (3 mg/kg i.v. or 10 mg/kg p.o.) prevented these changes in the ECG, while a potent vasodilator, papaverine, failed to do so. In the isolated, donor-perfused rat heart, SG-75 (1-30 micrograms) injected into the coronary perfusion system caused dose-dependent vasodilation, while 0.1-0.8 micrograms acetylcholine as well as methacholine produced marked vasoconstriction. SG-75 (10 mg/kg) administered orally to the donor rat inhibited the coronary vasoconstriction produced by the cholinomimetic drugs, whereas papaverine (30 micrograms i.a.) failed to prevent it. The inhibitory effects of SG-75 on methacholine-induced ECG changes in intact rats seemed to be due to its spasmolytic action.

Acetylcholine↗
PubMed1977

Purification and some properties of presumptive tof gene product of Coli phage 434.

The presumptive tof gene product of Coli phage 434 has been purified from cells carrying lambdaimm434cIdv plasmid known to contain only some of the "early" genes of phage 434 and lambda. It was detected and tentatively identified as tof protein primarily by its ability to specifically bind to phage 434 DNA. The protein has a molecular weight of about 11,000 and requires Mg2+ for specific DNA binding, unlike 434 cI-repressor.

Coliphages↗
PubMedDate not supplied

Species differences in renal vascular effects of dipyridamole and in the potentiation of adenosine action by dipyridamole.

The effects of dipyridamole and adenosine on the renal vasculature and on the enhancement by dipyridamole of the action of adenosine were studied in pigs, dogs, rabbits, and rats. Intravenous adenosine in doses of 10-300 micrograms/kg produced dose-dependent decreases in heart rate and blood pressure of rabbits and rats. Potentiation of adenosine action by intravenous infusion of dipyridamole occurred only in rabbits. When administered into the renal artery of pigs, dogs, rabbits, and rats, adenosine caused dose-dependent vasoconstriction in all species, whereas dipyridamole produced vasoconstriction in rabbits and vasodilation in pigs and rats. In dogs, the renal vascular response to dipyridamole depended on the perfusion method used. In kidneys perfused at a fixed flow rate with a pump, intrarenal dipyridamole elicited vasoconstriction, but in kidneys perfused by their own systemic blood pressure without the use of a pump, it caused vasodilation. The adenosine-induced renal vasoconstriction was enhanced by dipyridamole in pigs, dogs, and rabbits, but not in rats. Species differences and the perfusion method used are important for the renal vascular effects of dipyridamole. Dipyridamole appears to possess not only an indirect action on blood vessels which is related to adenosine, but also a direct vasodilator effect.

Adenosine↗
PubMedDate not supplied

Antihypertensive action of a novel orally active angiotensin converting enzyme inhibitor altiopril calcium (MC-838) in several hypertensive models of rats: comparison with captopril.

The antihypertensive effects of altiopril calcium (MC-838), calcium(-)-N-[(S)-3-[(N-cyclohexylcarbonyl-D-alanyl)thio]-2-methyl- propionyl]-L-prolinate, a novel inhibitor of angiotensin converting enzyme, compared with captopril, were evaluated in conscious rat models of experimental hypertension. MC-838 (3-30 mg/kg p.o.) as well as captopril (3 and 10 mg/kg p.o.) dose-dependently lowered systemic blood pressure (SBP) with no consistent changes in heart rate (HR) in two-kidney renal hypertensive rats (2 KG-RHRs) and spontaneously hypertensive rats (SHRs). However, MC-838 and captopril, unlike hydralazine, did not significantly produce hypotension in DOCA-salt hypertensive rats. The antihypertensive effect of MC-838, compared with captopril, was characterized by a slower onset and longer duration. When compared on a weight basis of 3 mg/kg, the antihypertensive effect of MC-838 was comparable to that of captopril in magnitude, but the duration of action was approximately 2 times longer than that of captopril. MC-838, like captopril, attenuated angiotensin-I (A-I)-induced pressor response, and augmented bradykinin (BK)-induced depressor one in SHRs. However, no correlation was observed between the modification of the SBP response to exogenous i.v. A-I or BK, and the SBP lowering caused by MC-838 or captopril given orally. In contrast, there was a close correlation between inhibition of lung angiotensin converting enzyme (ACE) (but not plasma ACE) and SBP reduction induced by the 2 ACE inhibitors in SHRs. When administered orally once a day for 9 weeks in 2 KG-RHRs and SHRs, MC-838 dose-dependently reduced SBP throughout the treatment period. After withdrawal of treatment with MC-838 there was no rebound increase in SBP. These studies indicate that MC-838 is a promising antihypertensive agent.

Angiotensin I↗