Chronic actions of a novel oral B-type natriuretic peptide conjugate in normal dogs and acute actions in angiotensin...

Area of Science:

• Cardiovascular Pharmacology
• Neuropeptide Therapeutics
• Renal Physiology

Background:

• Previous studies demonstrated the feasibility of acute, oral human B-type natriuretic peptide (hBNP).
• This study focuses on a new oral conjugated form, hBNP-054, for chronic administration.

Purpose of the Study:

• To evaluate the chronic effects of oral hBNP-054 on sodium excretion and blood pressure over 6 days.
• To assess the acute ability of hBNP-054 to activate cyclic guanosine monophosphate (cGMP) and reduce blood pressure in a model of angiotensin II-induced hypertension.

Main Methods:

• Developed and tested novel oral conjugated hBNP forms in dogs.
• Administered hBNP-054 chronically to normal dogs for 6 days.
• Investigated acute effects of hBNP-054 in dogs with angiotensin II-induced hypertension, measuring mean arterial pressure (MAP) and plasma cGMP.

Main Results:

• Chronic oral hBNP-054 reduced MAP for 6 days and increased 24-hour sodium excretion in normal dogs.
• Oral hBNP-054 was detected in plasma after administration, with peak levels at 30 minutes.
• In acute hypertension, hBNP-054 significantly increased plasma cGMP and reduced MAP for over 2 hours compared to vehicle.

Conclusions:

• A novel conjugated oral hBNP (hBNP-054) demonstrated sustained blood pressure-lowering and natriuretic effects.
• hBNP-054 activates cGMP and effectively reduces blood pressure in an acute hypertension model.
• Orally administered chronic hBNP represents a potential therapeutic strategy for cardiovascular diseases like hypertension.