β1-adrenergic receptor blockade attenuates angiotensin II-mediated catecholamine release into the cardiac interstitium in mitral regurgitation

Academic Article

Abstract

  • Background - This study tested the hypothesis that β1-adrenoreceptor blockade modulates the angiotensin II (Ang II)-evoked neural release of norepinephrine (NE) and epinephrine (Epi) into the cardiac interstitial fluid (ISF) space in experimentally induced mitral regurgitation (MR) in the dog. Methods and Results - Normal dogs (n=8) were compared with dogs with MR of 2 (n=8) and 4 (n=6) weeks' duration and with dogs with MR treated with β1-receptor blockade (RB; extended-release metoprolol succinate, 100 mg QD; MR+β1-RB) that was started 24 hours after MR induction for 2 (n=6) and 4 weeks (n=8). Left ventricular end-diastolic dimension increased 20% as plasma Ang II levels increased >5-fold in both MR and MR+β1-RB dogs at 2 and 4 weeks. Ang II infusion into the left atrium produced increases in ISF NE and Epi in normal dogs, which were further increased in 2- and 4-week MR dogs but were restored to normal in 4-week MR+β1-RB dogs. Ang II infusion produced 4-fold increases in circulating NE and Epi in 2- and 4-week MR dogs that returned to normal in 4-week+β1-RB dogs. Left ventricular angiotensin-converting enzyme activity and ISF Ang II were increased in 4-week MR dogs but were decreased in 4-week MR+β1-RB dogs. Conclusions - β1-RB decreases renin-angiotensin system sympathostimulation and activation by attenuating the Ang II-mediated NE and Epi release into the cardiac ISF and circulation and by decreasing left ventricular angiotensin-converting enzyme expression in the early phases of volume overload.
  • Published In

  • Circulation  Journal
  • Digital Object Identifier (doi)

    Author List

  • Tallaj J; Wei CC; Hankes GH; Holland M; Rynders P; Dillon AR; Ardell JL; Armour JA; Lucchesi PA; Dell'Italia LJ
  • Start Page

  • 225
  • End Page

  • 230
  • Volume

  • 108
  • Issue

  • 2