Effects of delapril on stroke, kidney dysfunction and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats.
This study was performed to investigate the beneficial effects of prolonged treatment with an angiotensin converting enzyme (ACE) inhibitor, delapril, on the appearance of symptoms of hypertensive cardiovascular disease in stroke-prone spontaneously hypertensive rats (SHRSP). Cardiovascular disease symptoms: stroke, kidney dysfunction and cardiac hypertrophy, were evaluated by monitoring the incidence of stroke signs, urinary excretion of protein and the heart weight, respectively. The SHRSP that were kept under salt-loaded conditions (1% NaCl drinking solution) from six weeks of age developed severe hypertension, showed an increased incidence of stroke signs and increased urinary excretion of protein. Long-term treatment with delapril (10mg/kg/day, p.o. for four weeks) decreased the blood pressure and completely inhibited the incidence of stroke signs and the increase in urinary excretion of protein. In SHRSP that were kept under normal conditions (without 1% NaCl drinking solution), long term treatment with delapril at the same dose decreased the heart weight and, after five weeks of treatment, left ventricular weight was decreased significantly and the wall/lumen ratio of small coronary arterioles and the thickness of the left ventricular wall were decreased slightly. These results indicate that delapril can prevent the development of symptoms of hypertensive cardiovascular diseases: stroke, kidney dysfunction and cardiac hypertrophy, with antihypertensive activity in SHRSP.
Inada
Y
Y
Pharmaceutical Research Division, Takeda Chemical Industries, Osaka, Japan.
Ojima
M
M
Itoh
K
K
Shino
A
A
Nishikawa
K
K
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004353:Drug Evaluation, Preclinical; D006973:Hypertension / Q000188:drug therapy*; D007189:Indans / Q000627:therapeutic use*; D008297:Male; D011507:Proteinuria / Q000517:prevention & control*; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D007189:Indans; C047759:delapril