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 |
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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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