Natriuretic+Peptides

__General Pharmacology__ Natriuretic peptides are peptide hormones that are synthesized by the heart, brain and other organs. [|Atrial natriuretic peptide] (ANP) is a 28 amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, [|angiotensin II] stimulation, [|endothelin], and [|sympathetic] stimulation ([|beta-adrenoceptor] mediated). Therefore, elevated levels of ANP are found during hypervolemic states (elevated blood volume) and congestive [|__heart failure__]. Brain-type natriuretic peptide (BNP; 32 amino acids), although first identified in the brain, is primarily produced by ventricular tissue in the heart, and like ANP, there is enhanced synthesis and release of BNP during heart failure. **Neutral endopeptidase** (NEP) is a circulating enzyme that degrades natriuretic peptides. Therefore, inhibition of this enzyme increases circulating levels of natriuretic peptide and potentiates their effects. //**Cardiovascular and renal effects.**// Natriuretic peptides are involved in the long-term regulation of sodium and water balance, blood volume and arterial pressure. These peptide hormones decrease aldosterone release by the adrenal cortex, increase glomerular filtration rate (GFR) and filtration fraction, produce natriuresis and diuresis (potassium sparing), and decrease [|__renin__] release, thereby decreasing circulating levels of [|__angiotensin II__]. These actions contribute to a reduction in [|blood volume] and therefore [|central venous pressure] (CVP), [|pulmonary capillary wedge pressure], [|cardiac output], and [|arterial blood pressure]. Chronic elevations of ANP appear to decrease arterial blood pressure primarily by decreasing systemic vascular resistance. The mechanism of systemic vasodilation involve ANP receptor-mediated elevations in vascular smooth muscle cGMP as well as by attenuating sympathetic vascular tone. This latter mechanism may involve ANP acting upon sites within the central nervous system as well as through inhibition of norepinephrine release by sympathetic nerve terminals. To summarize, //natriuretic peptides serve as a [|counter-regulatory system for the renin-angiotensin-aldosterone system]//. __Therapeutic Uses__ //**[|Heart failure].**// Heart failure leads to activation of the [|renin-angiotensin-aldosterone system], which causes increased sodium and water retention by the kidneys. This in turn increases blood volume and contributes to the elevated venous pressures associated with heart failure, which can lead to pulmonary and systemic edema. Increased angiotensin II also causes systemic vasoconstriction, which increases the afterload on the left ventricle. The primary use for diuretics in heart failure is to reduce pulmonary and/or systemic congestion and [|edema], and associated clinical symptoms (e.g., shortness of breath - dyspnea). Long-term treatment with diuretics may also reduce the [|afterload] on the heart by promoting systemic vasodilation, which can lead to improved ventricular ejection. __Specific Drugs__ Recombinant human BNP, or **nesiritide**, is approved for use in the acute treatment of decompensated congestive heart failure caused by systolic dysfunction. As a peptide, nesiritide has poor bioavailability and therefore is only available for intravenous administration. With a short half-life of less than 20 minutes, it is administered as a continuous infusion following a bolus injection. This drug is very effective in reducing [|pulmonary capillary wedge pressure] and improving dyspnea in this population of patients. __Adverse Side Effects and Contraindications__ The most prevalent side effect of nesiritide is hypotension, which can be long-lasted. Therefore, it is important to monitor arterial pressure during drug administration. Azotemia (an elevated blood level of urea or other nitrogen containing compounds) can occur in patients with renal disease in which kidney function depends on the activated renin-angiotensin-aldosterone system. This drug should not be used in patients having cardiogenic shock or having systolic pressures less than 90 mmHg. //Revised 12/15/05//
 * Natriuretic Peptides**