B-type Natriuretic Peptide (BNP) in Human Hypertension
| Status: | Archived |
|---|---|
| Conditions: | High Blood Pressure (Hypertension) |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
| Start Date: | February 2009 |
| End Date: | December 2011 |
Clinical Proteomics and Protein Therapeutics in Human Hypertension (BNP in Human Hypertension - Phase 1)
The investigators working hypothesis is that human hypertension is in part due to a
derangement in the endocrine function of the heart - a primary or secondary mechanism -
resulting in a relative deficiency of the natriuretic peptides (NP). The remodeled
hypertensive heart could result in altered processing and degradation of B-type NP resulting
in altered molecular forms with decreased biological activity. The investigators further
hypothesized the chronic administration of BNP in subjects with hypertension, is feasible,
safe and will induce a sustained reduction in blood pressure.
Ongoing investigations by our laboratory group and others have established that the heart is
an endocrine organ as well as a pump. The heart synthesizes and secretes two peptide
hormones - atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) - that are
endogenous ligands for a particulate guanylyl cyclase receptor (NPR-A). Following receptor
binding and generation of its second messenger cGMP, the natriuretic peptides (NPs) mediate
biological actions which include natriuresis, inhibition of the renin-angiotensin system and
vasodilatation with local autocrine and paracrine actions in the heart to include inhibition
of fibrosis and enhancement of diastolic function.
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, ANP and BNP synthesis and secretion occur contributing to maintenance of
optimal cardiorenal and blood pressure homeostasis.
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