{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T04:17:49Z","timestamp":1743394669710,"version":"3.40.3"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2000,1]]},"abstract":"<jats:p><jats:italic>Abstract<\/jats:italic>\u2014\u03b2-Blockers are widely used for hypertension treatment but must be taken daily. We have developed a novel \u03b2-blocker by targeting \u03b2<jats:sub>1<\/jats:sub>-adrenergic receptor (\u03b2<jats:sub>1<\/jats:sub>-AR) mRNA with antisense oligodeoxynucleotides (\u03b2<jats:sub>1<\/jats:sub>-AS-ODN). A single intravenous injection of \u03b2<jats:sub>1<\/jats:sub>-AS-ODN significantly reduced cardiac contractility and blood pressure (38\u00b15 mm Hg,<jats:italic>P<\/jats:italic>&lt;0.05) in spontaneously hypertensive rats for 3 weeks. In the present study, we improved the antihypertensive effect of \u03b2<jats:sub>1<\/jats:sub>-AS-ODN by delivery with the cationic liposomes DOTAP\/DOPE and studied its impact on the peripheral renin-angiotensin system. Five charge ratios (\u00b1) of liposome\/ODN from 0 to 3.5 were tested to deliver 0.5 mg\/kg \u03b2<jats:sub>1<\/jats:sub>-AS-ODN intravenously in spontaneously hypertensive rats (n=30). On the basis of the magnitude and duration of hypotension, 2.5 was determined to be the optimal charge ratio, which decreased blood pressure by up to 35 mm Hg for 20 to 33 days (<jats:italic>P<\/jats:italic>&lt;0.05). The effects were specific for \u03b2<jats:sub>1<\/jats:sub>-AR, because radioligand binding assay and quantitative autoradiography showed a 35% reduction in \u03b2<jats:sub>1<\/jats:sub>-AR levels in kidney but no change in \u03b2<jats:sub>2<\/jats:sub>-AR. \u03b2<jats:sub>1<\/jats:sub>-AS-ODN diminished the preprorenin mRNA levels in renal cortex by 37% 4 days after administration. This transient effect was followed by a delayed yet marked diminution of plasma renin activity and plasma angiotensin II levels on days 10 and 17 (<jats:italic>P<\/jats:italic>&lt;0.01). The results show that \u03b2<jats:sub>1<\/jats:sub>-AS-ODN has an effective long-term antihypertensive effect up to 33 days with a single intravenous injection. The mechanism appears to be through reduced \u03b2<jats:sub>1<\/jats:sub>-AR number specifically and reduced cardiac contractility. The inhibition of the renin-angiotensin system is probably a second mechanism to produce the sustained antihypertensive effect of \u03b2<jats:sub>1<\/jats:sub>-AS-ODN.<\/jats:p>","DOI":"10.1161\/01.hyp.35.1.219","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"219-224","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["New \u03b2-Blocker"],"prefix":"10.1161","volume":"35","author":[{"given":"Yuan","family":"Clare Zhang","sequence":"first","affiliation":[{"name":"From the Department of Physiology, School of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Birgitta","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, School of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leping","family":"Shen","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, School of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Ian","family":"Phillips","sequence":"additional","affiliation":[{"name":"From the Department of Physiology, School of Medicine, University of Florida, Gainesville."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/1.1.91"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1994.444"},{"key":"e_1_3_2_3_2","unstructured":"Zhang YC Bui JD Shen L Phillips MI. Antisense inhibition of \u03b21-adrenoceptor mRNA in a single dose produces a profound and prolonged reduction in high blood pressure in spontaneously hypertensive rats. Circulation. 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