Ray Kanagawa, Takeo Wada, Tsukasa Sanada, Mami Ojima and Yoshiyuki Inada
Pharmaceutical Research Laboratories II, Pharmaceutical Research Division,
Takeda Chemical Industries, Ltd., 17-85, Jusohonmachi 2-chome, Yodogawa-ku,
Osaka 532, Japan
Abstract: The regional hemodynamic effects of candesartan cilexetil
(TCV-116), a selective angiotensin II AT1-receptor antagonist, and enalapril,
an angiotensin-converting enzyme inhibitor, were compared in conscious spontaneously
hypertensive rats (SHR). A 7-day repeated administration study was carried
out. TCV-116 (1 mg/kg, p.o.) and enalapril (10 mg/kg, p.o.) reduced blood
pressure to the same extent 5 hr after administration on the 1st and the
7th day. At these points, the cardiac index and organ or tissue blood flow
were measured by the non-radioactive colored dye-extraction microsphere
technique. Repeated administration of TCV-116, and single and repeated administration
of enalapril significantly increased renal blood flow without any changes
in the cardiac index. TCV-116 and enalapril also tended to increase splanchnic
blood flow following the 1st dose but not the 7th dose. No significant changes
in blood flow were observed in the brain, heart, adrenal, skin and skeletal
muscle. These results suggest that the antihypertensive effects of TCV-116
and enalapril are attributable to the systemic reduction of vascular resistance
caused by the dilatation of blood vessels. These hemodynamic effects of
TCV-116, like those of enalapril, may be beneficial in the treatment of
hypertension.
Keywords: Angiotensin II receptor antagonist, Candesartan cilexetil (TCV-116),
Enalapril, Spontaneously hypertensive rat, Blood flow