Molecular Mechanism of Blood Pressure Regulation through the Atrial Natriuretic Peptide.
Takeshi TokudomeKentaro OtaniPublished in: Biology (2022)
Natriuretic peptides, including atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP), have cardioprotective effects and regulate blood pressure in mammals. ANP and BNP are hormones secreted from the heart into the bloodstream in response to increased preload and afterload. Both hormones act through natriuretic peptide receptor 1 (NPR1). In contrast, CNP acts through natriuretic peptide receptor 2 (NPR2) and was found to be produced by the vascular endothelium, chondrocytes, and cardiac fibroblasts. Based on its relatively low plasma concentration compared with ANP and BNP, CNP is thought to function as both an autocrine and a paracrine factor in the vasculature, bone, and heart. The cytoplasmic domains of both NPR1 and NPR2 display a guanylate cyclase activity that catalyzes the formation of cyclic GMP. NPR3 lacks this guanylate cyclase activity and is reportedly coupled to G i -dependent signaling. Recently, we reported that the continuous infusion of the peptide osteocrin, an endogenous ligand of NPR3 secreted by bone and muscle cells, lowered blood pressure in wild-type mice, suggesting that endogenous natriuretic peptides play major roles in the regulation of blood pressure. Neprilysin is a neutral endopeptidase that degrades several vasoactive peptides, including natriuretic peptides. The increased worldwide clinical use of the angiotensin receptor-neprilysin inhibitor for the treatment of chronic heart failure has brought renewed attention to the physiological effects of natriuretic peptides. In this review, we provide an overview of the discovery of ANP and its translational research. We also highlight our recent findings on the blood pressure regulatory effects of ANP, focusing on its molecular mechanisms.
Keyphrases
- blood pressure
- hypertensive patients
- heart rate
- ejection fraction
- atrial fibrillation
- wild type
- amino acid
- small molecule
- bone mineral density
- induced apoptosis
- heart failure
- low dose
- left ventricular
- nitric oxide
- type diabetes
- blood glucose
- magnetic resonance imaging
- left atrial
- high throughput
- white matter
- transcription factor
- endoplasmic reticulum stress
- multidrug resistant
- contrast enhanced
- soft tissue
- escherichia coli
- cell cycle arrest
- cerebral ischemia
- replacement therapy
- klebsiella pneumoniae
- brain injury
- functional connectivity
- cell death
- signaling pathway
- biofilm formation