From the Guidelines
Nesiritide causes natriuresis by mimicking the actions of naturally occurring B-type natriuretic peptide (BNP) in the body, leading to increased urinary sodium excretion and urine output. When administered, nesiritide binds to natriuretic peptide receptors in the kidneys, which activates guanylyl cyclase and increases intracellular cyclic guanosine monophosphate (cGMP) levels, as described in the guidelines for the diagnosis and management of heart failure 1. This biochemical cascade leads to several renal effects that promote sodium and water excretion.
- Specifically, nesiritide increases glomerular filtration rate by dilating the afferent arterioles and constricting the efferent arterioles of the glomerulus, which increases the filtration pressure.
- It also directly inhibits sodium reabsorption in the proximal tubule and collecting duct of the nephron.
- Additionally, nesiritide counteracts the renin-angiotensin-aldosterone system by reducing renin secretion, which further decreases sodium retention, as noted in the management of acute heart failure 1.
- It also antagonizes the antidiuretic effects of vasopressin, allowing for greater free water excretion. These combined mechanisms result in increased urinary sodium excretion (natriuresis) and increased urine output (diuresis), making nesiritide useful in managing fluid overload in conditions like acute decompensated heart failure, as approved for use in the management of acute HF 1.
From the Research
Mechanism of Natriuresis
Nesiritide causes natriuresis through several mechanisms:
- Reduction of preload and afterload, leading to decreased pulmonary capillary wedge pressure and pulmonary artery pressure 2, 3
- Suppression of the renin-angiotensin-aldosterone system (RAAS) and endothelin-1, resulting in decreased aldosterone levels 2, 3, 4, 5
- Increase in cardiac index and stroke volume index, without increasing heart rate 2, 4
- Balanced vasodilation of arteries and veins, leading to improved hemodynamics 4
Effects on Neurohormonal Responses
Nesiritide has been shown to:
- Decrease plasma renin, aldosterone, norepinephrine, and endothelin-1 levels 2, 3, 4
- Reduce ventricular ectopy and ventricular tachycardia 2
- Improve heart rate variability 2
- Decrease plasma aldosterone values when administered alone or in combination with furosemide 5
Comparison with Other Treatments
Nesiritide has been compared to other treatments, such as:
- Furosemide, which produces natriuresis/diuresis and a prompt rise in plasma aldosterone values, whereas nesiritide alone produces no significant natriuresis/diuresis but decreases plasma aldosterone values 5
- Nitroglycerin, which has less robust effects on pulmonary capillary wedge pressure compared to nesiritide 3