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.