Document Detail


A novel atrial natriuretic peptide based therapeutic in experimental angiotensin II mediated acute hypertension.
MedLine Citation:
PMID:  20975033     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
M-atrial natriuretic peptide (ANP; M-ANP) is a novel next generation 40 amino acid peptide based on ANP, which is highly resistant to enzymatic degradation and has greater and more sustained beneficial actions compared with ANP. The current study was designed to advance our understanding of the therapeutic potential of M-ANP in a canine model of acute angiotensin II-induced hypertension with elevated cardiac filling pressures and aldosterone activation. We compare M-ANP with vehicle and equimolar human B-type natriuretic peptide, which possesses the most potent in vivo actions of the native natriuretic peptides. M-ANP significantly lowered mean arterial pressure and systemic vascular resistance. Importantly, despite a reduction in blood pressure, renal function was enhanced with significant increases in renal blood flow, glomerular filtration rate, diuresis, and natriuresis after M-ANP infusion. Although angiotensin II induced an acute increase in pulmonary capillary wedge pressure, M-ANP significantly lowered pulmonary capillary wedge pressure, pulmonary artery pressure, and right atrial pressure. Further, M-ANP significantly suppressed angiotensin II-induced activation of aldosterone. These cardiovascular and renal enhancing actions of M-ANP were accompanied by significant increases in plasma and urinary cGMP, the second messenger molecule of the natriuretic peptide system. When compared with human B-type natriuretic peptide, M-ANP had comparable cardiovascular actions but resulted in a greater natriuretic effect. These results suggest that M-ANP, which is more potent than ANP in normal canines, has potent blood pressure lowering and renal enhancing properties and may, therefore, serve as an ANP based therapeutic for acute hypertension.
Authors:
Paul M McKie; Alessandro Cataliotti; Guido Boerrigter; Horng H Chen; S Jeson Sangaralingham; Fernando L Martin; Tomoko Ichiki; John C Burnett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-10-25
Journal Detail:
Title:  Hypertension     Volume:  56     ISSN:  1524-4563     ISO Abbreviation:  Hypertension     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-18     Completed Date:  2010-12-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906255     Medline TA:  Hypertension     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1152-9     Citation Subset:  IM    
Affiliation:
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. mckie.paul@mayo.edu
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Aldosterone / analysis
Angiotensin II / pharmacology
Animals
Antihypertensive Agents / pharmacology
Atrial Natriuretic Factor / metabolism,  therapeutic use*
Blood Pressure / drug effects
Cyclic GMP / blood,  urine
Diuresis / drug effects
Dogs
Glomerular Filtration Rate / drug effects
Humans
Hypertension / chemically induced,  drug therapy*
Male
Natriuresis / drug effects
Pulmonary Wedge Pressure / drug effects
Renal Circulation / drug effects
Vascular Resistance / drug effects
Grant Support
ID/Acronym/Agency:
P01 HL76611/HL/NHLBI NIH HHS; R01 HL 36634/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Antihypertensive Agents; 11128-99-7/Angiotensin II; 52-39-1/Aldosterone; 7665-99-8/Cyclic GMP; 85637-73-6/Atrial Natriuretic Factor

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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