Compartmentalization of angiotensin II generation in the dog heart: Evidence for independent mechanisms in intravascular and interstitial spaces

Academic Article

Abstract

  • Angiotensin-converting enzyme inhibitors have beneficial effects that are presumably mediated by decreased angiotensin II (ANG II) production. In this study, we measure for the first time ANG I and ANG II levels in the interstitial fluid (ISF) space of the heart. ISF and aortic plasma ANG I and II levels were obtained at baseline, during intravenous infusion of ANG I (5 μM, 0.1 ml/min, 60 min), and during ANG I + the angiotensin-converting enzyme inhibitor captopril (cap) (2.5 mM, 0.1 ml/min, 60 min) in six anesthetized open-chested dogs. ISF samples were obtained using microdialysis probes inserted into the left ventricular myocardium (3-4 probes/dog). ANG I increased mean arterial pressure from 102±3 (SEM) to 124±3 mmHg (P < 0.01); addition of cap decreased MAP to 95±3 mmHg (P < 0.01). ANG I infusion increased aortic plasma ANG I and ANG II (pg/ml) (ANG I = 101±129 to 370±158 pg/ml, P < 0.01; and ANG II = 22±40 to 466±49, P < 0.01); addition of cap further increased ANG I (1,790±158, P < 0.01) and decreased ANG II (33±49, P < 0.01). ISF ANG I and ANG II levels (pg/ml) were > 100-fold higher than plasma levels, and did not change from baseline (8,122±528 and 6,333±677), during ANG I (8,269±502 and 6,139±695) or ANG I + cap (8,753±502 and 5,884±695). The finding of very high ANG I and ANG II levels in the ISF vs. intravascular space that are not affected by IV ANG I or cap suggests that ANG II production and/or degradation in the heart is compartmentalized and mediated by different enzymatic mechanisms in the interstitial and intravascular spaces.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Pubmed Id

  • 26187106
  • Author List

  • Dell'Italia LJ; Meng QC; Balcells E; Wei CC; Palmer R; Hageman GR; Durand J; Hankes GH; Oparil S
  • Start Page

  • 253
  • End Page

  • 258
  • Volume

  • 100
  • Issue

  • 2