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Y Inada

Publications and source records attributed to Y Inada.

At least 253 records · Page 14Linked to original sources
PubMed1986

Antihypertensive action of a non-sulfhydryl angiotensin converting enzyme inhibitor (CV-3317) in various hypertensive models.

The antihypertensive action of N-[N-[(S)-1-ethoxycarbonyl-3-phenyl-propyl]-L-alanyl]-N-(indan-2-yl) glycine hydrochloride (CV-3317), a nonsulfhydryl compound characterized as an angiotensin converting enzyme inhibitor in our previous work, was examined in hypertensive animal models. In 2-kidney, 1 clip hypertensive rats and dogs, CV-3317 (3 and/or 10 mg/kg, p.o.) produced a sustained antihypertensive action of about 15 to 25 mmHg. Daily oral administrations of CV-3317 (1 to 10 mg/kg/day) to spontaneously hypertensive rats (SHR) for 5 weeks produced a sustained antihypertensive action of 20 to 40 mmHg. When CV-3317 (3 mg/kg) was combined with hydrochlorothiazide (10 mg/kg), its antihypertensive action was intensified in potency and duration. CV-3317 (30 mg/kg) induced a slight hypotension (5 to 10 mmHg) in normotensive rats, but had no effect on the blood pressure of 1-kidney, 1 clip hypertensive rats and on that of a low renin type of DOCA/salt hypertensive rat. The antihypertensive activity of CV-3317 was more potent than that of captopril. In pithed SHR, the pressor response induced by an electrical stimulation of the preganglionic sympathetic nerve, but not the pressor response to norepinephrine, was attenuated by both agents (0.3 mg/kg, i.v.). Both agents may exert their antihypertensive action not only primarily by inhibiting the renin-angiotensin system, but also by inhibiting norepinephrine release from the sympathetic nerve terminals indirectly by reducing the formation of vascular angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1986

Inhibition of angiotensin converting enzyme by CV-3317, a non-sulfhydryl compound.

N-[N-[(S)-1-Ethoxycarbonyl-3-phenylpropyl]-L-alanyl]-N-(indan-2- yl)glycine hydrochloride (CV-3317) and its de-esterified products, CV-3317-COOH and CV-3317-(5-OH)-COOH, inhibited rabbit lung angiotensin converting enzyme (ACE) with the IC50s of 1.2 X 10(-7), 4.0 X 10(-8) and 4.9 X 10(-8) M, respectively, angiotensin I (A-I)-induced vasoconstriction of the rat aorta (IC50: 2.6 X 10(-7), 2.6 X 10(-8) and 5.4 X 10(-8) M, respectively), and A-I-induced pressor response of the rat kidney (IC50: 3.9 X 10(-7), 3.5 X 10(-8) and 2.8 X 10(-8) M, respectively). In these 3 experiments, both de-esterified products were 4 to 14 times more potent than captopril. In rats, CV-3317 (0.0138 to 138 mumol/kg, p.o.) inhibited plasma and lung ACEs, and the effects at a dose of 0.46 mumol/kg lasted more than 8 hr. CV-3317 inhibited the A-I-induced pressor action in rats (0.138 to 13.8 mumol/kg, p.o. or 0.046 to 0.138 mumol/kg i.v.) and dogs (0.46 to 4.6 mumol/kg, p.o.) in a dose-related manner. CV-3317 was more potent and longer acting than captopril in these in vivo ACE inhibitions. CV-3317 augmented bradykinin-induced hypotension (dogs) and contraction of the ileum (guinea pigs) less potently than captopril. In spontaneously hypertensive rats (SHR), CV-3317 (3 mg/kg, p.o.) markedly inhibited plasma and tissue (aorta, kidney, lung and brain) ACEs; and when administered daily for 2 weeks, it inhibited the plasma, aorta, kidney and lung ACEs; in particular, it markedly inhibited the aortic ACE. Captopril (30 mg/kg, p.o.) markedly inhibited tissue ACEs and slightly plasma ACE, but its inhibitory effects on tissue ACEs, except for the aorta, were unclear by repeated dosings and its effect on plasma ACE was rather enhanced. Thus, the inhibition of vascular ACE may be particularly important for the antihypertensive effect of the ACE inhibitors, including CV-3317, in SHR.

Angiotensin I↗
PubMed1986

Characterization of polyethylene glycol-modified L-asparaginase from Escherichia coli and its application to therapy of leukemia.

For the purpose of clinical application to the therapy of human leukemia and lymphosarcoma, L-asparaginase from Escherichia coli was modified with 2,4-bis(O-methoxypolyethylene glycol)-6-chloro-s-triazine (activated PEG2) by an improved method, which involves a purification step of activated PEG2 by gel filtration. The PEG2-modified asparaginase retained approximately 30% (73 IU/mg of protein) of the enzymic activity of the native enzyme, while it had almost wholly lost the immunoreactivity towards anti-asparaginase antibodies. The modified enzyme retained the characteristics of the native enzyme in terms of the pH- and temperature-dependencies of activity and stability, and the Km value for L-asparagine. Administration of the modified enzyme to a dog with spontaneous lymphosarcoma induced complete remission without any toxic side effects. Seven children with multiple relapses of acute leukemia were treated with a regimen of cycles of methotrexate and native asparaginase. Three of these children developed anaphylactic shock. In contrast to the native enzyme, the successive administration of PEG2-modified asparaginase to those three patients was therapeutically effective without causing any allergic reaction.

Adolescent↗
PubMed1986

[Air scalers].

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Air↗