Hypertension and Angiotensin II Hypersensitivity in Aminopeptidase A—deficient Mice

• DOI: 10.1007/bf03402108
• Publication Date: 2018-09-07T02:59:33Z
• Authors: Takashi Mitsui; Seiji Nomura; Mayumi Okada; Yasumasa Ohno; Honami Kobayashi; Yutaka Nakashima; Yasutaka Murata; Mikihito Takeuchi; Naohiko Kuno; Tetsuo Nagasaka; Jiyang O-Wang; Max D. Cooper; Shigehiko Mizutani
• Keywords: Homeostasis

Local concentrations of the vasopressor peptide, angiotensin II (AngII), depend upon balance between synthesis and degradation. Previous studies blood pressure (BP) regulation have focused primarily on generation AngII its receptors, less attention has been devoted to Aminopeptidase A (APA, EC 3.4.11.7) is responsible for N-terminal cleavage AngII, a hydrolytic event that serves as rate-limiting step in To evaluate physiological role APA, we examined BP homeostasis APA-deficient mice. We measured basal with continuous infusion APA mutant mice by tail-cuff method. also evaluated development histology AngII-targeted organs well urine excretion these Homozygous were found elevated systolic when compared heterozygous wild-type littermate Infusion led an enhanced response Despite sustained elevation knockout mice, neither their renal cardiac sizes nor histological appearances not different from control Moreover, volume, osmolality, electrolyte content normal deficiency increased baseline hypertensive levels AngII. These findings indicate lowering offer novel insight into mechanisms developing hypertension.