ANP

ANP binds NPR-A, a single-transmembrane receptor with intrinsic guanylyl cyclase activity. Ligand binding activates the cytoplasmic guanylyl cyclase domain, generating cGMP. Elevated cGMP activates PKG, which phosphorylates targets in vascular smooth muscle (causing relaxation and vasodilation), renal tubular cells (increasing sodium excretion), and adrenal glomerulosa cells (suppressing aldosterone synthesis).

In the kidney, ANP increases glomerular filtration rate by dilating the afferent arteriole while constricting the efferent arteriole. ANP directly inhibits sodium reabsorption in the inner medullary collecting duct and suppresses renin release, reducing angiotensin II and aldosterone to further decrease sodium retention. The net result is increased urine output and reduced circulating volume, lowering preload and blood pressure.

Carperitide (ANP) infusion in acute decompensated heart failure reduces pulmonary capillary wedge pressure, systemic vascular resistance, and dyspnea. Clinical trials in Japan demonstrated superiority over standard therapy in reducing cardiac workload. The drug has been in clinical use in Japan for heart failure for over two decades.

Low-dose ANP infusion has been investigated for prevention of contrast-induced nephropathy and ischemic acute kidney injury. Small trials showed reduced creatinine elevation and better renal function preservation when ANP was infused perioperatively during cardiac surgery with high AKI risk.

ANP reduces infarct size in ischemia-reperfusion models through cGMP-mediated cardioprotective mechanisms similar to nitric oxide signaling. Pre-conditioning with ANP activates PKG and reduces mitochondrial permeability transition pore opening during reperfusion.