Journal
HYPERTENSION
Volume 78, Issue 6, Pages 1859-1867Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.121.17159
Keywords
aldosterone; blood pressure; cardiovascular disease; guanylyl cyclase; natriuresis
Categories
Funding
- Mayo Clinic
- Broadview Ventures
- [RO1 HL136340]
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MANP is a novel ANP analog with potent pharmacological effects, showing potential therapeutic effects for patients with hypertension.
M-atrial natriuretic peptide (MANP) is a novel ANP (atrial natriuretic peptide) analog engineered to be an innovative particulate GC-A (guanylyl cyclase A) receptor activator. The rationale for its design was to develop a best-in-class GC-A activator with enhanced cGMP activating, natriuretic, aldosterone-suppressing, and blood pressure-lowering actions, compared with endogenous ANP, for the treatment of hypertension. Here, we report the first-in-human study on the safety, tolerability, neurohumoral, renal, and blood pressure-lowering properties of MANP in hypertension subjects. This was an open-label sequential single ascending dose design in which all subjects stopped all antihypertensive agents for 14 days before receiving a single subcutaneous injection of MANP. MANP was safe, well tolerated, activated cGMP, induced natriuresis, reduced aldosterone, and decreased blood pressure at or below the maximal tolerated dose. Thus, MANP has a favorable safety profile and produced expected pharmacological effects in human hypertension. Our results support further investigations of MANP as a potential future blood pressure-lowering, natriuretic and aldosterone-suppressing drug for hypertension especially resistant hypertension.
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