Aminopeptidase N in arterial hypertension.
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.
Danziger
Robert S
RS
Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA. Rdanziger@aol.com
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology; D000805:Angiotensin III / Q000378:metabolism / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018826:CD13 Antigens / Q000378:metabolism* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology*; D051381:Rats; D020303:Rats, Inbred Dahl; D011918:Rats, Inbred SHR
D000804:Angiotensin II; D000805:Angiotensin III; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; D018826:CD13 Antigens