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• W2027134610 abstract "Background: The objective of the current study was to establish the chronic diuretic actions of a novel oral conjugated human BNP (hBNP-054) and to define its blood pressure lowering effects in a model of hypertension (HTN). Methods: First we tested hBNP-054 both acutely and chronically in normal dogs to assess its biological actions as a blood pressure lowering agent and as a natriuretic factor. Secondly, we investigated the effects of acute oral hBNP-054 or vehicle in dogs that received concomitant continuous intravenous infusion of angiotensin II (ANG II). After baseline (BL) determination of mean blood pressure (MAP) and blood collection for plasma hBNP and cGMP, all dogs received continuous ANG II infusion (20 μg/kg/min, 1 ml/min) for 4 hrs to induce HTN. After 30 min of ANG II administration, dogs received oral hBNP-054 (400 μg/kg) or vehicle in a random crossover fashion with a one week interval between dosing. Blood sampling and MAP measurements were repeated 30 min after ANG II and 10, 30, 60, 120, 180 and 240 min after oral administration of hBNP-054 or vehicle. Results: In the chronic study, oral hBNP-054 effectively reduced MAP for 6 days and it induced a significant increase in 24-hr sodium excretion. hBNP was not present in the plasma at BL in any dogs, and it was not detected at any time in the vehicle group. However, hBNP was detected throughout the duration of the study after oral hBNP-054 with a peak concentration at 30 min of 1060±818 pg/ml. After ANG II administration, plasma cGMP was not activated after vehicle, while it was significantly increased after oral hBNP-054 (p<0.0001 between two groups). Importantly, MAP was significantly increased after ANG II throughout the study protocol. However, while no changes occurred in MAP after vehicle administration, oral hBNP-054 was followed by a significant reduction in MAP for over 2 hrs (from 138±1 after ANG II to 124±2 and 130±5 mmHg 1 and 2 hrs after oral hBNP-054 respectively; p<0.001). Conclusion: For the first time we report that a novel oral hBNP has blood pressure lowering effects over a 6-day period and natriuretic actions when administered chronically. Furthermore, hBNP-054 activates cGMP and significantly reduces MAP in a model of acute HTN." @default.
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• W2027134610 date "2008-08-01" @default.
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• W2027134610 title "A Novel Orally Active BNP Possesses Chronic Natriureti Actions, Decreases Mean Arterial Pressure and Activates cGMP in a Model of Acute Hypertension" @default.
• W2027134610 doi "https://doi.org/10.1016/j.cardfail.2008.06.421" @default.
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