Natriuretic peptides - Physiology & Variations

 Studies conducted in the 1950s, revealed that dilatation of the cardiac atria could induce natriuresis. In 1964, electron microscopy revealed the presence of secretory granules in the atrial myocyte.In 1981 de Bold and colleagues demonstrated that extracts from atrial myocytes injected into rats led to brisk natriuresis and diuresis. These atrial hormones were subsequently named atrial natriuretic peptides(ANP)
The Brain natriuretic peptide (BNP) was discovered from porcine brain in 1988. BNP is first synthesized as prepro-BNP, which is then cleaved to pro-BNP(108 aa) and finally to BNP (32 aa). The remaining 76 aa N terminal unit is called the NT-pro BNP. Both BNP and NT-pro BNP are sensitive diagnostic markers for heart failure.




Eventhough both of them can be used for diagnosing heart failure, they have different ranges, cut off values and certain physiological differences.  
BNP is a biologically active neurohormone whereas NT-pro BNP circulates as a inert substance.The clearance mechanisms and half-lives of BNP and NT-proBNP are also different. BNP is degraded by endopeptidases and has a half-life of 5–10 min, whereas NT-proBNP is cleared passively primarily by the kidney and has a half-life of 25–120 min.Despite these notable differences, the two hormones share many similarities in terms of their utility for diagnosis and risk stratification.


Variations in levels : Natriuretic peptide levels have been shown to fluctuate on a day-to-day basis and are correlated with a variety of characteristics. In a study including 911 healthy subjects(with normal LVEF) from the Framingham Heart study cohort, the strongest predictor of a high BNP/NT-pro BNP were older age and female sex. Other predictors for high peptide levels were lower diastolic blood pressure, lower BMI, and a large left atrial size.

As we all know, obesity is associated with higher incidence of Hypertension.The mechanism is likely due to sodium/water retention. If this is true then they might have an inherent low BNP level( also called natriuretic handicap). This was shown nicely...again in a group of Framingham patients that healthy! people who are obese have a low BNP/NT pro BNP. Also patients with Diabetes have a low peptide level. Obesity and Diabetes together have an additive effect on lowering BNP levels.


when intrepreting peptide levels, we should have these physiological variations in mind before making decisions based on BNP/NT-pro BNP levels.