atrial-natriuretic-factor and Metabolic-Diseases

Atrial natriuretic peptide (ANP) is a cardiac hormone with pleiotropic cardiovascular and metabolic properties including vasodilation, natriuresis and suppression of the renin-angiotensin-aldosterone system. Moreover, ANP induces lipolysis, lipid oxidation, adipocyte browning and ameliorates insulin sensitivity. Studies on ANP genetic variants revealed that subjects with higher ANP plasma levels have lower cardio-metabolic risk. In vivo and in humans, augmenting the ANP pathway has been shown to exert cardiovascular therapeutic actions while ameliorating the metabolic profile. MANP is a novel designer ANP-based peptide with greater and more sustained biological actions than ANP in animal models. Recent studies also demonstrated that MANP lowers blood pressure and inhibits aldosterone in hypertensive subjects whereas cardiometabolic properties of MANP are currently tested in an on-going clinical study in hypertension and metabolic syndrome. Evidence from in vitro, in vivo and in human studies support the concept that ANP and related pathway represent an optimal target for a comprehensive approach to cardiometabolic disease.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Genetic Variation; Humans; Metabolic Diseases; Molecular Targeted Therapy

Atrial natriuretic factor (ANF) is the first of a group of atrial natriuretic peptides (ANPs) discovered since 1981. This group of peptides is thought to have an important role in sodium homeostasis and regulation of fluid volume. Although the role of ANF in cardiovascular and renal disorders is under investigation, the specific signaling involvement that ANF may have in the central nervous system is still unexplored. To date, ANF has not as yet been associated with a given functional area in the brain, nor has it been shown to be linked to any particular psychopathology. Neuropharmacology research of these peptides and their drug manipulation is needed to advance our knowledge of the possible role of ANF in psychiatry beyond the current level of speculation.

Topics: Atrial Natriuretic Factor; Brain; Drinking Behavior; Humans; Mental Disorders; Metabolic Diseases; Neurosecretory Systems; Vasopressins; Water; Water-Electrolyte Balance

Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis and energy balance; dysfunction of these critical processes underpins obesity and contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, and immune cell reactivity. Herein, we investigated a parallel, preservative function for CNP in coordinating metabolic homeostasis. Global inducible CNP knockout mice exhibited reduced body weight, higher temperature, lower adiposity, and greater energy expenditure in vivo. This thermogenic phenotype was associated with increased expression of uncoupling protein-1 and preferential lipid utilization by mitochondria, a switch corroborated by a corresponding diminution of insulin secretion and glucose clearance. Complementary studies in isolated murine and human adipocytes revealed that CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming via Gi-coupled natriuretic peptide receptor (NPR)-C and reducing peroxisome proliferator-activated receptor-γ coactivator-1α expression, while concomitantly driving adipogenesis via NPR-B/protein kinase-G. Finally, we identified an association between CNP/NPR-C expression and obesity in patient samples. These findings establish a pivotal physiological role for CNP as a metabolic switch to balance energy homeostasis. Pharmacological targeting of these receptors may offer therapeutic utility in the metabolic syndrome and related cardiovascular disorders.

Topics: Animals; Atrial Natriuretic Factor; Cardiovascular Diseases; Homeostasis; Metabolic Diseases; Mice; Mice, Knockout; Natriuretic Peptide, C-Type; Receptors, Atrial Natriuretic Factor; Thermogenesis

A 49-year-old man had sudden chest pain and paralysis of the lower right limb. An acute aortic dissection was diagnosed in a computed tomography scan and the patient underwent an emergency operation. After the operation, myonephropathic metabolic syndrome developed, and human atrial natriuretic peptide was administered for 11 days until the volume of daily urine output reached at least 10,000 mL, which would facilitate limb salvage and the preservation of life without hemodialysis. This report documents that postoperative myonephropathic metabolic syndrome improved due to the strong diuretic action of human atrial natriuretic peptide without hemodialysis.

Topics: Acute Disease; Aortic Aneurysm, Thoracic; Aortic Dissection; Atrial Natriuretic Factor; Blood Vessel Prosthesis Implantation; Dose-Response Relationship, Drug; Follow-Up Studies; Humans; Infusions, Intravenous; Male; Metabolic Diseases; Middle Aged; Postoperative Complications; Radiography; Rhabdomyolysis; Syndrome

Circulating immunoreactive atrial natriuretic peptide, IrANP(99-126) and the N-terminal fragment of the prohormone, IrANP(1-98) were measured in two population samples from the general population of Gothenburg, Sweden. A group of 85-year olds (974 subjects) and a group of 40-year olds (191 subjects) were investigated in respect of cardiovascular, renal and metabolic disease. IrANP(99-126) and IrANP(1-98) were significantly higher in the 85-year olds compared to the 40-year olds, and were significantly increased in subjects with congestive heart failure, ischaemic heart disease, atrial fibrillation and renal dysfunction but not in subjects with hypertension. Eighty-five-year-old subjects who were on treatment with digitalis, beta-adrenergic-blockers, nitrates and diuretics had significantly increased IrANP(99-126) and IrANP(1-98). In multivariate analysis IrANP(99-126) concentrations were predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation and treatment with beta-blockers and anti-depressant drugs. IrANP(1-98) was predictive for congestive heart failure, ischaemic heart disease, atrial fibrillation, diabetes mellitus, renal failure and drug treatment with beta-blockers and neuroleptics. We conclude that measurements of circulating concentrations of IrANP(99-126) and/or IrANP(1-98) may add valuable information in the diagnosis of congestive heart failure and ischaemic heart disease in an elderly population. It remains to be determined whether routine measurements of circulating IrANP (99-126) and IrANP(1-98) may be of value in predicting current cardiovascular disease for the individual patient.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Cardiovascular Diseases; Female; Heart Diseases; Humans; Kidney Diseases; Male; Metabolic Diseases; Peptide Fragments; Protein Precursors