Hypertension remains a global burden in cardiovascular disease leading to stroke, myocardial
infarction, and heart failure. Its myocardial complications result from increased mechanical
load on the heart. Under physiological conditions of increased myocardial load and resulting
myocardial stretch, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)
synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood
pressure homeostasis. However, studies indicate that in subjects with cardiovascular diseases
the biological structure of these hormones may be altered, thus reducing their favorable
protective activities. New studies indicate that early and moderate hypertension is
associated with a derangement of the natriuretic peptide system which is characterized by the
lack of activation of biologically active ANP and BNP, while severe hypertension is
characterized by cardiac release of altered molecular forms of ANP and BNP that have reduced
biological properties and/or enhanced degradation.
The broad objective of this proposal is to advance the biology and therapeutics of the NPs
with a special focus on the cardiac peptide BNP in human hypertension. Our proposal is based
upon the biological properties of BNP (i.e. natriuretic, renin-angiotensin-aldosterone
suppressing, vasodilating, anti-fibrotic, anti-hypertrophic and positive lusitropic), its
mechanistic role in human hypertension, and thus its potential as an innovative chronic
protein therapeutic to enhance the treatment of patients with hypertension. Importantly, BNP
is an endocrine hormone normally produced by the human heart, and it has been approved for
the treatment of acute heart failure in USA.