ANP

**Source and stimulus:** Synthesized by atrial cardiac myocytes (stored as pro-ANP) and released in response to atrial distension from increased intravascular volume (e.g., heart failure, high-salt intake, supine position/water immersion). BNP is similar but released from ventricles in response to ventricular stretch.

**Mechanism:** ANP binds natriuretic peptide receptor-A (NPR-A), a membrane-bound guanylyl cyclase, which increases cGMP and activates PKG. (Contrast with NO, which raises cGMP via soluble guanylyl cyclase.)

**Effects:** - Kidney: afferent arteriole dilation and efferent arteriole constriction raise GFR and filtration fraction. It also inhibits Na+ reabsorption in the collecting duct (inner medullary collecting duct), causing natriuresis and diuresis. - Inhibits renin secretion, aldosterone release (adrenal zona glomerulosa), and ADH effects, so it opposes the RAAS. - Vasculature: smooth muscle relaxation (venous > arterial) lowers preload and BP. It also increases capillary permeability, shifting fluid out of the vasculature.

**Degradation:** Neprilysin (neutral endopeptidase) breaks down ANP and BNP. Sacubitril inhibits neprilysin and is combined with valsartan (ARNI) for HFrEF. Do not combine it with an ACE inhibitor because of the risk of angioedema (bradykinin buildup).

**Clinical correlations:** - Heart failure: ANP and BNP are elevated. BNP and NT-proBNP are used for diagnosis and for distinguishing cardiac from pulmonary dyspnea. Nesiritide is recombinant BNP. - "Aldosterone escape": in primary hyperaldosteronism, volume expansion raises ANP, which limits Na+ retention. This explains why edema is absent and hypernatremia is mild or absent, with hypertension and hypokalemia. - SIADH/hyponatremia: ANP contributes to natriuresis in conditions such as subarachnoid hemorrhage (cerebral salt wasting, via BNP/ANP). - Atrial myxoma and tachyarrhythmias (e.g., SVT) can raise ANP, causing polyuria. - Mnemonic: ANP = "Atrial Natriuretic Peptide" gives Na+ loss, vasodilation, ↓ preload, ↓ BP; it acts as a "physiologic diuretic" counterbalancing the RAAS.

**High-yield comparison:** ANP and BNP lower BP through the NPR-A/cGMP pathway. Angiotensin II, aldosterone, and ADH oppose them by promoting Na+ and water retention and vasoconstriction.