Obsah

In vivotransfer of antisense oligonucleotide against urinary kininase blunts deoxycorticosterone acetate-salt hypertension in rats

Autor: Masataka Majima, Naruya Tomita, Ryuichi Morishita, Toshiaki Okumura, Izumi Hayashi, Jitsuo Higaki, Tomoe Fujita, Ogiwara Toshio, Yuji Kumagai
Rok vydání: 2000
Předmět:
Zdroj: British Journal of Pharmacology. 131:820-826
ISSN: 0007-1188
DOI: 10.1038/sj.bjp.0703634
Popis: We have previously reported that the renal kallikrein-kinin system suppressed the development of deoxycorticosterone acetate (DOCA)-salt hypertension. Kinins were degraded in the kidney mainly by carboxypeptidase Y (CPY)-like kininase. Blockade of renal kinin degradation may reduce hypertension in the developmental stage. We constructed an antisense oligonucleotide against rat CPY homologue (5'-CAT-CTC-TGC-TTC-CTT-GTG-TC-3', AS) and its randomized control oligonucleotide (5'-TCC-TTC-CTG-CTT-GAG-TTC-CT-3', RC), and prepared an HVJ-liposome complex that prolongs and increases the effectiveness of the antisense oligonucleotide. Antisense oligonucleotide was transfected (25 nmole rat(-1), in terms of nucleotide) into the kidney from the renal artery. Blood pressure was measured through a catheter inserted into the abdominal aorta. Mean blood pressure (MBP) in DOCA-salt treated (for 2 weeks) Sprague Dawley strain rats was 130+/-3 mmHg (n=11), and was reduced significantly (P
Databáze: OpenAIRE
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