A novel atrial natriuretic peptide based therapeutic in experimental angiotensin II mediated acute hypertension.
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.
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA. mckie.paul@mayo.edu
Paul M
PM
McKie
Alessandro
A
Cataliotti
Guido
G
Boerrigter
Horng H
HH
Chen
S Jeson
SJ
Sangaralingham
Fernando L
FL
Martin
Tomoko
T
Ichiki
John C
JC
Burnett
D000208:Acute Disease; D000450:Aldosterone / Q000032:analysis; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D000804:Angiotensin II; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP