Natriuretic Peptides and Blood Pressure Homeostasis: Implications for MANP, a Novel Guanylyl Cyclase a Receptor Activator for Hypertension

Valentina Cannone,John C Burnett

doi:10.3389/fphys.2021.815796

Abstract

The heart serves as an endocrine organ producing the hormones atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP) which via the guanylyl cyclase A (GC-A) receptor and the second messenger cGMP participate in blood pressure homeostasis under physiologic conditions. Genetic models of the ANP gene or the GCA receptor together with genomic medicine have solidified the concept that both cardiac hormones are fundamental for blood pressure homeostasis and when deficient or disrupted they may contribute to human hypertension. Advances in peptide engineering have led to novel peptide therapeutics including the ANP-analog MANP for human hypertension. Most importantly a first in human study of MANP in essential hypertension has demonstrated its unique properties of aldosterone suppression and blood pressure reduction. Physiology and pharmacology ultimately lead us to innovative peptide-based therapeutics to reduce the burden of cardiovascular disease.

Highlights

Hypertension still represents the leading cause of death worldwide
This challenge is highlighted in a report from the National Institutes of Health Working Group in Hypertension which called for new research regarding mechanisms and novel therapies especially in the setting of difficult to control hypertension such as resistant hypertension (Sigmund et al, 2020)
In this Review we will highlight the physiology of the heart as an endocrine organ producing the two important blood pressure lowering hormones atrial natriuretic peptide (ANP) and b-type natriuretic peptide (BNP)

Summary

Introduction

Hypertension still represents the leading cause of death worldwide. Importantly, ranking number two in cause of death is metabolic disease including diabetes and obesity both of which are predisposing and coexisting factors for hypertensive disease (Foreman et al, 2018).

Results

Conclusion