Tissue distribution of CysAP activity and its relationship to blood pressure and water balance

Life Sci. 2015 Aug 1:134:73-8. doi: 10.1016/j.lfs.2015.04.023. Epub 2015 May 23.

Abstract

Aims: To better understand the functional role of soluble (Sol) and membrane-bound (MB) cystinyl-aminopeptidase (CysAP) activities, we studied differentially their organ distribution in adult male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR)with or without treatment with captopril.We searched for a possible tissue-specific association of CysAP with water balance and blood pressure.

Main methods: We used twenty WKY rats distributed in ten controls and ten captopril-treated, and sixteen SHR divided in eight controls and eight captopril-treated. Captopril (100 mg/kg/day) was administered in drinking water for 4 weeks. Systolic blood pressure, water intake and diuresis were measured individually. CysAP was assayed fluorometrically using L-cystine-di-β-naphthylamide as substrate.

Key findings: Sol or MB activities were generally higher in SHR compared to WKY notably in hypothalamus and kidney than in the other tissues. Captopril mainly decreased CysAP in SHR whereas it increased in WKY. The distribution of Sol CysAP was more homogeneous among tissues ofWKY than SHR. In contrast, the distribution of MB CysAP was more heterogeneous than Sol CysAP in both WKY and SHR. This suggests that MB CysAP activity acts in a more tissue-specific manner than Sol CysAP. The majority of the significant correlations between tissue activities and the measured physiological parameters were observed mostly in renal medulla and hypothalamus.

Significance: Sol and MB CysAP activities, acting separately or in concert and mainly in renal medulla, regulate the function of their susceptible endogenous substrates, and may participate meaningfully in the control of blood pressure and fluid balance.

Keywords: Membrane-bound fraction; Oxytocinase; Placental leucine aminopeptidase; Soluble fraction; Vasopressinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Blood Pressure / drug effects
  • Blood Pressure / physiology*
  • Captopril / pharmacology
  • Cystinyl Aminopeptidase / metabolism*
  • Hippocampus / enzymology*
  • Kidney Medulla / enzymology*
  • Male
  • Organ Specificity / drug effects
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Water-Electrolyte Balance / drug effects
  • Water-Electrolyte Balance / physiology*

Substances

  • Antihypertensive Agents
  • Captopril
  • Cystinyl Aminopeptidase