Protective effects of candesartan cilexetil (TCV-116) against stroke, kidney dysfunction and cardiac hypertrophy in stroke-prone spontaneously hypertensive rats.
The effects of chronic treatment with an angiotensin II receptor antagonist, candesartan cilexetil (TCV-116, 0.1, 1, 10 mg/kg), and an angiotensin converting enzyme inhibitor, enalapril maleate (enalapril, 10 mg/kg), on the development of end-organ damage were examined in stroke-prone spontaneously hypertensive rats (SHRSP). The control SHRSP developed severe hypertension with stroke signs and increased urinary protein excretion. TCV-116 (0.1 mg/kg) reduced the stroke incidence and urinary protein excretion without affecting the blood pressure. TCV-116 (1 and 10 mg/kg) and enalapril reduced blood pressure, the stroke incidence, the urinary indices and left ventricular weight. Circulating renin-angiotensin system (RAS) and renal renin mRNA expression were significantly accelerated or tended to be accelerated in the control SHRSP with end-organ damages. A low dose of TCV-116 tended to reduce the RAS indices in plasma by improving the damages, whereas a high dose (10 mg/kg) increased them by the reflexes with blocking RAS. The present results indicate that chronic All blockade reduces the increase in blood pressure, end-organ damages and RAS related to the damages in SHRSP.
Inada
Y
Y
Pharmaceutical Research laboratories II, Takeda Chemical Industries Ltd., Osaka, Japan.
Wada
T
T
Ojima
M
M
Sanada
T
T
Shibouta
Y
Y
Kanagawa
R
R
Ishimura
Y
Y
Fujisawa
Y
Y
Nishikawa
K
K
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000809:Angiotensins / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D004656:Enalapril / Q000494:pharmacology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011945:Receptors, Angiotensin / Q000235:genetics; D012083:Renin / Q000235:genetics / Q000378:metabolism; D013777:Tetrazoles
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000809:Angiotensins; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000808:Angiotensinogen; D004656:Enalapril; D012083:Renin; C077793:candesartan cilexetil