Angiotensinase and Vasopressinase Activities in Hypothalamus, Plasma, and Kidney after Inhibition of Angiotensin-converting Enzyme: Basis for a New Working Hypothesis

 

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Abstract

Reducing angiotensin II (Ang II) production via angiotensin-converting enzyme (ACE) inhibitors is a key approach for the treatment of hypertension. However, these inhibitors may also affect other enzymes, such as angiotensinases and vasopressinase, responsible for the metabolism of other peptides also involved in blood pressure control, such as Ang 2-10, Ang III, Ang IV, and vasopressin. We analyzed the activity of these enzymes in the hypothalamus, plasma, and kidney of normotensive adult male rats after inhibition of ACE with captopril. Aspartyl- (AspAP), glutamyl- (GluAP), alanyl- (AlaAP) and cystinyl-aminopeptidase (CysAP) activities were measured fluorimetrically using arylamides as substrates. Systolic blood pressure (SBP), water intake, and urine flow were also measured. Captopril reduced SBP and increased urine flow. In the hypothalamus, GluAP and AspAP increased, without significant changes in either AlaAP or CysAP. In contrast with effects in plasma, GluAP was unaffected, AspAP decreased, while AlaAP and CysAP increased. In the kidney, enzymatic activities did not change in the cortex, but decreased in the medulla. These data suggest that after ACE inhibition, the metabolism of Ang I in hypothalamus may lead mainly to Ang 2-10 formation. In plasma, the results suggest an increased formation of Ang IV together with increased vasopressinase activity. In the kidney, there is a reduction of vasopressinase activity in the medulla, suggesting a functional reduction of vasopressin in this location. The present data suggest the existence of alternative pathways in addition to ACE inhibition that might be involved in reducing BP after captopril treatment.

^‡  In memoriam

• References

• 1 Paul M, Poyan Mehr A, Kreutz R. Physiol Rev 2006; 86: 747-803
  CrossrefPubMed
• 2 Ferrario CM. Curr Opin Nephrol Hypertens 2011; 20: 1-6
  CrossrefPubMed
• 3 Banegas I, Prieto I, Vives F, Alba F, de Gasparo M, Segarra AB, Hermoso F, Durán R, Ramírez M. J Renin Angiotensin Aldosterone Syst 2006; 7: 129-134
  CrossrefPubMed
• 4 Stragier B, De Bundel D, Sarre S, Smolders I, Vauquelin G, Dupont A, Michotte Y, Vanderheyden P. Heart Fail Rev 2008; 13: 321-337
  CrossrefPubMed
• 5 Wang DH, Prewitt RL. Am J Physiol 1991; 260: H1959-H1965
  PubMed
• 6 Segarra AB, Ramírez M, Villarejo AB, Banegas I, Vives F, de Gasparo M, Alba F, Cobo J, Prieto I. Horm Metab Res 2010; 42: 222-224
  Article in Thieme ConnectPubMed
• 7 Prieto I, Segarra AB, Vargas F, Alba F, de Gasparo M, Ramirez M. Horm Metab Res 2003; 35: 279-281
  Article in Thieme ConnectPubMed
• 8 Segarra AB, Ramírez M, Banegas I, Hermoso F, Vargas F, Vives F, Alba F, de Gasparo M, Prieto I. Horm Metab Res 2006; 38: 48-52
  Article in Thieme ConnectPubMed
• 9 Wallis MG, Lankford MF, Keller SR. Am J Physiol Endocrinol Metab 2007; 293: E1092-E1102
  CrossrefPubMed
• 10 Albiston AL, Yeatman HR, Pham V, Fuller SJ, Diwakarla S, Fernando RN, Chai SY. Regul Pept 2011; 166: 83-89
  CrossrefPubMed