Effects of allisartan, a new AT(1) receptor blocker, on blood pressure and end-organ damage in hypertensive animals.
OBJECTIVE
To investigate the effects of allisartan, a new angiotensin II type 1 (AT(1)) receptor antagonist, on blood pressure (BP) and end-organ damage (EOD) in hypertensive rats and dogs.


METHODS
First, a single dose of allisartan was given intragastrically to evaluate the BP reduction in spontaneously hypertensive rats (SHRs), two kidney-one clip (2K1C) renovascular hypertensive rats and dogs, and Beagle dogs with angiotensin II-induced hypertension. Second, allisartan was mixed in rat chow for long-term treatment. After 4 months of drug administration, rats were instrumented to determine BP and baroreflex sensitivity (BRS). Observation of morphologic changes was used to estimate EOD. Third, the acute toxicity of allisartan was compared with that of losartan in mice.


RESULTS
BP was significantly decreased after intragastric administration of allisartan in SHRs, 2K1C rats, 2K1C dogs and Beagle dogs with angiotensin II-induced hypertension. Compared with the control, SHRs that received long-term treatment with allisartan exhibited an improved BRS and organ protective effects. Mice who were administered allisartan experienced less acute toxicity than those treated with losartan.


CONCLUSIONS
Allisartan is highly effective for BP reduction and organ protection with low toxicity.
Wu
Ming-yue
MY
Department of Pharmacology, Second Military Medical University, Shanghai, China.
Ma
Xiu-juan
XJ
Yang
Chu
C
Tao
Xia
X
Liu
Ai-jun
AJ
Su
Ding-feng
DF
Liu
Jian-guo
JG
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology* / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000473:pathology; D007668:Kidney / Q000473:pathology; D019808:Losartan / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D051379:Mice; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley
D047228:Angiotensin II Type 1 Receptor Blockers; D019808:Losartan