Human Hypertension Is Characterized by a Lack of Activation of the Antihypertensive Cardiac Hormones ANP and BNP

Abstract

Objectives This study sought to investigate plasma levels of circulating cardiac natriuretic peptides, atrial natriuretic peptide (ANP) and B-type or brain natriuretic peptide (BNP), in the general community, focusing on their relative differences in worsening human hypertension. Background Although ANP and BNP are well-characterized regulators of blood pressure in humans, little is known at the population level about their relationship with hypertension. The authors hypothesized that hypertension is associated with a lack of activation of these hormones or their molecular precursors. Methods The study cohort (N = 2,082, age>45 years) was derived from a random sample from Rochester, Minnesota, and each subject had a medical history, clinical examination, and assessment of different plasma forms of ANP and BNP. Patients were stratified by blood pressure. Multivariable linear regression was used to assess differences in natriuretic peptide levels in worsening hypertension. Results Compared to normotensive, BNP1–32 and N-terminal proBNP1–76 (NT-proBNP1–76) were significantly decreased in pre-hypertension (p < 0.05), with BNP1–32 significantly decreased in stage 1 as well (p < 0.05). Although proBNP1–108 remained unchanged, the processed form was significantly increased only in stage 2 hypertension (p < 0.05). ANP1–28 remained unchanged, while NT-ANP1–98 was reduced in pre-hypertension (p < 0.05). Conclusions The authors demonstrated the existence of an impaired production and/or release of proBNP1–108 along with a concomitant reduction of BNP1–32 and NT-proBNP1–76 in the early stages of hypertension, with a significant elevation only in stage 2 hypertension. Importantly, they simultaneously demonstrated a lack of compensatory ANP elevation in advanced hypertension.

Efficacy and Safety of LCZ696, a First-in-Class Angiotensin Receptor Neprilysin Inhibitor, in Asian Patients With Hypertension

“…Levels of NPs may be decreased in some hypertensive states. 4 Neprilysin degrades NPs, and inhibition of neprilysin increases NP levels.5 However, the BP reductions observed with neprilysin inhibition alone are modest.6,7 Concomitant neprilysin inhibition and RAS suppression have effects on sodium and volume excretion and BP reductions to a greater extent compared with RAS inhibitors alone. …”

“…Levels of NPs may be decreased in some hypertensive states. 4 Neprilysin degrades NPs, and inhibition of neprilysin increases NP levels.…”

Deletion of Rictor in Brain and Fat Alters Peripheral Clock Gene Expression and Increases Blood Pressure

“…Our results obtained in mice are in agreement with the findings in a study with patients showing that a prehypertensive state is associated with a deficiency of circulating brain NP levels. 25 Interestingly, low plasma levels of NPs have been identified as a common predisposition for metabolic and cardiovascular diseases. 19 In line with data from hyperinsulinemic rats displaying a hypertensive phenotype, 26 we showed that in Rictor aP2KO mice hyperinsulinemia is associated with increased HR and blood pressure.…”

Innovative Strategy in Therapy of Cardiac Insufficiency

“…Показано, что при артериальной гипертонии (АГ) наблюдается дефицит НУП, приводящий к нарушению натрийуреза; при хронической сердечной недостаточности (ХСН) также наблюдается дисбаланс гормонов системы НУП [21][22][23][24][25][26][27][28]. Поэтому синтез ингиби-торов НЭП -значимый шаг в фармакотерапии сердечно-сосудистых заболеваний, в частности СН.…”