Effects of Glycosylated Atrial Natriuretic Peptide on Blood Pressure and Fluid Balance in Healthy Volunteers
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 17
- Locations
- 1
Study Overview
Brief Summary
The human heart produces hormones that help regulate blood pressure and fluid balance in the body. One of these hormones is atrial natriuretic peptide (ANP). ANP lowers blood pressure by relaxing blood vessels and increasing urinary excretion by the kidneys.
Previous research has demonstrated that ANP naturally carries a small sugar molecule attached. This sugar moiety is produced endogenously and can modify the biological activity of ANP. When this sugar is present, ANP may affect blood vessels and renal function differently compared with the non-glycosylated form.
The present study examines how this sugar modification alters the physiological effects of ANP. This is achieved by administering ANP, either with or without the attached sugar molecule, via intravenous infusion. The study aims to determine whether glycosylated ANP differs from the native form in its effects on blood pressure and fluid balance.
Detailed Description
Introduction Atrial natriuretic peptide (ANP) is a critical component of the natriuretic peptide family and plays a central role in cardiovascular homeostasis. ANP is primarily synthesized and secreted by atrial myocytes in response to atrial stretch and related stimuli. The peptide exerts biological effects through binding to specific receptors, leading to activation of A-type guanylyl cyclase (GC) (also known as NPR-A) and subsequent production of cyclic guanosine monophosphate (cGMP). This signaling cascade induces vasodilation, natriuresis, and diuresis, thereby contributing to regulation of blood pressure and fluid balance.
The concept of proteoforms refers to the various molecular forms that a protein can assume, arising from genetic variation, alternative splicing, and post-translational modification. ANP proteoforms therefore comprise molecular variants of ANP with potentially distinct biological activities and clinical implications.
ANP proteoforms have diagnostic and prognostic value in cardiovascular disease. Elevated ANP and related peptides indicate increased cardiac stress and are observed in conditions such as heart failure, hypertension, and acute coronary syndromes. Measurement of ANP, together with B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP), is widely used in clinical practice to assist diagnosis and guide management (Volpe 2021).
Beyond diagnostic utility, ANP possesses therapeutic potential. Vasodilatory and natriuretic properties make ANP an attractive candidate for treatment of conditions associated with fluid overload and hypertension. Recombinant ANP analogues have been used clinically in acute heart failure.
Recent advances highlight strategies to enhance natriuretic peptide activity. Inhibition of neprilysin prolongs peptide half-life and biological effect. Combined neprilysin inhibition and angiotensin receptor blockade has demonstrated clinical benefit in heart failure (McMurray 2013).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 30 Years (Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Healthy male volunteers
- •Age: 18-30 years
- •BMI: 20-25 kg/m²
- •Body weight ≤90 kg (amended protocol)
- •Normal hemoglobin
- •Ability to provide informed consent
Exclusion Criteria
- •Acute illness within two weeks
- •Chronic cardiovascular, renal, hepatic, pulmonary, metabolic or malignant disease
- •Hypotension or history of syncope
- •Substance or alcohol abuse
- •Recent blood donation (<3 months)
- •Medication that cannot be safely interrupted
Investigators
Peter Fruergaard Andersen
MD
University of Copenhagen