{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T15:09:23Z","timestamp":1761059363391},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Heart Failure"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:sec>\n            <jats:title>Background\u2014<\/jats:title>\n            <jats:p>The (pro)renin receptor (P)RR is implicated in blood pressure regulation and the pathophysiology of heart failure (HF). The effects of (P)RR blockade in HF have not been previously investigated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and Results\u2014<\/jats:title>\n            <jats:p>\n              Eight sheep received on 2 separate days a vehicle control and incremental intravenous boluses of a (P)RR antagonist, ovine handle region peptide (HRP) (1, 5, and 25 mg at 90-minute intervals), both before (normal) and after induction of HF by rapid left ventricular pacing. In normal sheep, HRP reduced heart rate (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) and hematocrit (\n              <jats:italic>P<\/jats:italic>\n              =0.019) compared with time-matched control data, without significantly affecting any other hemodynamic, hormonal, or renal variables. In sheep with HF, HRP treatment induced progressive falls in mean arterial pressure (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001) in association with decreases in left atrial pressure (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), peripheral resistance (\n              <jats:italic>P<\/jats:italic>\n              =0.014), and hematocrit (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). Cardiac contractility tended to decline (\n              <jats:italic>P<\/jats:italic>\n              =0.096), whereas cardiac output was unaltered. HRP administration produced a dose-dependent decrease in plasma renin activity (\n              <jats:italic>P<\/jats:italic>\n              =0.004), with similar trends observed for plasma angiotensin II and aldosterone (\n              <jats:italic>P<\/jats:italic>\n              =0.093 and\n              <jats:italic>P<\/jats:italic>\n              =0.088, respectively). Circulating natriuretic peptides, endothelin-1, and catecholamine levels were unchanged. HRP also induced a reduction in plasma sodium concentrations relative to control (\n              <jats:italic>P<\/jats:italic>\n              =0.024), a natriuresis (\n              <jats:italic>P<\/jats:italic>\n              =0.046), and a tendency for creatinine excretion and clearance to improve.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>(P)RR antagonism in experimental HF resulted in cardiovascular and renal benefits in association with inhibition of the renin-angiotensin-aldosterone system. These findings suggest that (P)RR contributes to pressure\/volume regulation in HF and identifies the receptor as a potential therapeutic target in this disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circheartfailure.112.967059","type":"journal-article","created":{"date-parts":[[2012,7,14]],"date-time":"2012-07-14T09:47:35Z","timestamp":1342259255000},"page":"645-652","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Hemodynamic, Hormonal, and Renal Effects of (Pro)Renin Receptor Blockade in Experimental Heart Failure"],"prefix":"10.1161","volume":"5","author":[{"given":"Miriam T.","family":"Rademaker","sequence":"first","affiliation":[{"name":"From the Christchurch Heart Institute, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim G.","family":"Yandle","sequence":"additional","affiliation":[{"name":"From the Christchurch Heart Institute, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leigh J.","family":"Ellmers","sequence":"additional","affiliation":[{"name":"From the Christchurch Heart Institute, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher J.","family":"Charles","sequence":"additional","affiliation":[{"name":"From the Christchurch Heart Institute, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. Gary","family":"Nicholls","sequence":"additional","affiliation":[{"name":"From the Christchurch Heart Institute, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. Mark","family":"Richards","sequence":"additional","affiliation":[{"name":"From the Christchurch Heart Institute, University of Otago, Christchurch, New Zealand."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1000638"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199108013250501"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0895-7061(96)00092-1"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e3283060f2e"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214276"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1159\/000220260"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.12.050"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000199912.47657.04"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119000"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000215838.48170.0b"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.1.220"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2009.09.015"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00055.2008"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.107.101493"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI21398"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006010029"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080820"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2741\/e156"},{"issue":"4","key":"e_1_3_4_20_2","first-page":"H1052","article-title":"Neurohumoral changes during onset and offset of ovine heart failure: role of ANP.","volume":"256","author":"Fitzpatrick MA","year":"1989","unstructured":"Fitzpatrick MA, Nicholls MG, Espiner EA, Ikram H, Bagshaw P, Yandle TG. 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