Pharmacological Studies on (4S)-1-Methyl-3-{(2S)-2-[N-((1S)-1-Ethoxycarbonyl-3-Phenylpropyl)amino] Propionyl}-2-Oxolmidazolidine-4-Carboxylic Acid Hydrochloride (TA-6366), a New ACE Inhibitor: I. ACE Inhibitory and Anti-Hypertensive Activities

et al. 1994

ABSTRACT-Ourprevious studies showed that imidapril prevented the occurrence of cerebral stroke and ameliorated biochemical parameter changes of renal dysfunction at a dose that did not inhibit the progres sion of hypertension in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). To confirm these findings, a histopathological investigation was conducted on the kidney of salt-loaded (from 11 to 16 weeks of age) SHRSP, which was the subject of the preceding study. Their brains and hearts were also ex amined. Histopathologically, renal lesions such as fibrinoid necrosis and proliferative arteritis of small calibration arteries, necrotizing glomerulitis and tubular degeneration, and cerebral hemorrhage and slight cardial hypertrophy were observed in salt-loaded control SHRSP. The occurrence of these lesions were prevented in a dose-dependent manner by the administration of imidapril (1 and 2 mg/kg/day). Especially, the preventive effects on the renal lesions were apparently noted. Enalapril also prevented these renal lesions, but its preventive effects were weaker than those of imidapril at the same dose (2 mg/kg/day). It became evident from the results of the present and previous studies that imidapril reduced renal biochemical and histopathological injuries.

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mentioning

confidence: 97%

Histopathological Investigation on Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats, Whose Biochemical Parameters of Renal Dysfunction Were Ameliorated by Administration of Imidapril

Fujiwara¹,

Yuasa²,

et al. 1994

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“…and in two kidney one clip renal hypertensive rats at more than 0.5 mg/kg, p.o. (5). In SHRSP maintained on a 1 o-NaCl drinking solu tion, which is an accelerator of stroke incidence (6,7), the preventive effect on stroke was not equipotent between the two agents.…”

mentioning

confidence: 98%

Influence of Imidapril on Abnormal Biochemical Parameters in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats (SHRSP)

Sumikawa

Minamide

et al. 1993

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ABSTRACT-Many of the disorders in urinary, biochemical, and hematological parameters induced by salt-loading in stroke-prone spontaneously hypertensive rats (SHRSP) were significantly ameliorated by chronic treatment with angiotensin converting enzyme inhibitors, imidapril (1 and 2 mg/kg) and enalapril (2 mg/kg). Through the improvement of these parameters, the treatment reduced the incidence of stroke but did not suppress the development of hypertension. These results suggest that the prophylaxis of stroke in SHRSP is probably due to systemic improvement as judged from the parameters of renal functions.

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“…The antihypertensive effect of imidapril was known to be as potent as that of enalapril and 5 times more potent than that of captopril in some experimental hypertensive animal models (9). However, the effective imidapril dose for increasing the life-span in (W X B)F 1 males was 5 mg/kg/day, p.o., which was almost equal to that of cap topril.…”

Section: Hypertensionmentioning

confidence: 98%

Reduction of the Mortality Rate by Imidapril in a Small Coronary Artery Disease Model, (NZW x BXSB)F1 Male Mice

Sumikawa

Nishimura

et al. 1994

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