The effect of recombinant aminopeptidase A on hypertension in spontaneously hypertensive rats: its effect in comparison with candesartan.
An understanding of aminopeptidase A in hypertension is important, given its ability to cleave the N-terminal aspartic acid of potent vasoconstrictor angiotensin II. However, the role of aminopeptidase A in hypertension has received limited attention. Because we have succeeded in producing recombinant human aminopeptidase A, the effect of aminopeptidase A on systolic blood pressure in the spontaneously hypertensive rat was examined. Aminopeptidase A of 0.016 mg/kg was administrated intravenously to spontaneously hypertensive rats and blood pressure was monitored for 72 h. For repeated administration, aminopeptidase A doses of 0.016 mg/kg and 0.1-mg/kg doses of candesartan (an angiotensin II receptor 1 subtype blocker) were administrated daily in spontaneously hypertensive rats and blood pressure was monitored for 5 d. Bolus intravenous injection of aminopeptidase A at a dose of 0.016 mg/kg significantly decreased systolic blood pressure for 36 h in spontaneously hypertensive rats. A comparison of the antihypertensive effects of aminopeptidase A versus candesartan in spontaneously hypertensive rats showed that the effective dose of aminopeptidase A was about one-tenth that of candesartan. These results suggest the novel approach of utilizing aminopeptidase A to treat hypertension by degrading circulating angiotensin II before it binds to the receptor 1 subtype.
Ishii
M
M
Department of Medical Science of Proteases, Nagoya University School of Medicine, Nagoya, Japan. masai@med.nagoya-u.ac.jp
Hattori
A
A
Numaguchi
Y
Y
Tsujimoto
M
M
Ishiura
S
S
Kobayashi
H
H
Murohara
T
T
Wright
J-W
JW
Mizutani
S
S
D000803:Angiotensin I / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents; D016367:Baculoviridae / Q000235:genetics; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D005822:Genetic Vectors; D043384:Glutamyl Aminopeptidase / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009154:Mutation; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D013777:Tetrazoles / Q000494:pharmacology*
D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011994:Recombinant Proteins; D013777:Tetrazoles; D000804:Angiotensin II; D009599:Nitroprusside; D000803:Angiotensin I; D043384:Glutamyl Aminopeptidase; C081643:candesartan