Aminopeptidase N in arterial hypertension

• Published in: Heart failure reviews Vol. 13; no. 3; pp. 293 - 298
• Main Author: Danziger, Robert S.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.09.2008; Springer Nature B.V
• Subjects: Aminopeptidase; Angiotensin; Angiotensin II - analogs & derivatives; Angiotensin II - metabolism; Angiotensin II - physiology; Angiotensin III; Angiotensin III - metabolism; Angiotensin III - physiology; Animals; ANP gene; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; Cardiology; CD13 antigen; CD13 Antigens - metabolism; CD13 Antigens - therapeutic use; Central nervous system; Enkephalins; Humans; Hypertension; Hypertension - drug therapy; Hypertension - enzymology; Hypertension - physiopathology; Medicine; Medicine & Public Health; Metalloproteinase; Neuropeptides; Pathogenesis; Rats; Rats, Inbred Dahl; Rats, Inbred SHR; Somatostatin; Therapeutic targets; Hypertension; Aminopeptidase N
• ISSN: 1382-4147; 1573-7322
• DOI: 10.1007/s10741-007-9061-y

Aminopeptidase N (APN) or CD13 is a conserved type II integral membrane zinc-dependent metalloprotease in the M1 family of ectoenzymes. APN is abundant in the kidneys and central nervous system. Identified substrates include Angiotensin III (Ang III); neuropeptides, including enkephalins and endorphins; and homones, including kallidan and somatostatin. It is developmentally expressed, a myelomonocytic marker for leukemias, and a receptor for coronovirus. There is evolving support for APN in the regulation of arterial blood pressure and the pathogenesis of hypertension. In rodent strains, intracerebraventricular (i.c.v.) infusions of APN reduces, while inhibitors of APN activity have a pressor effect on blood pressure. Dysregulation of central APN has been linked to the pathogenesis of hypertension in the spontaneously hypertensive rat. There is evidence that renal tubule APN inhibits Na flux and plays a mechanistic role in salt-adaptation. A functional polymorphism of the ANP gene has been identified in the Dahl salt-sensitive rat. Signaling by APN impacting on blood pressure is likely mediated by regulation of the metabolism of Ang III to Ang IV. Whether APN regulates arterial blood pressure in humans or is a therapeutic target for hypertension are subjects for future exploration.