Hyperaldosteronism induces left atrial systolic and diastolic dysfunction.
Patients with hypertension and hyperaldosteronism show an increased risk of stroke compared with patients with essential hypertension. Aim of the study was to assess the effects of aldosterone on left atrial function in rats as a potential contributor to thromboembolism. Osmotic mini-pumps delivering 1.5 μg aldosterone/h were implanted in rats subcutaneously (Aldo, n = 39; controls, n = 38). After 8 wk, left ventricular pressure-volume analysis of isolated working hearts was performed, and left atrial systolic and diastolic function was also assessed by atrial pressure-diameter loops. Moreover, left atrial myocytes were isolated to investigate their global and local Ca2+handling and contractility. At similar heart rates, pressure-volume analysis of isolated hearts and in vivo hemodynamic measurements revealed neither systolic nor diastolic left ventricular dysfunction in Aldo. In particular, atrial filling pressures and atrial size were not increased in Aldo. Aldo rats showed a significant reduction of atrial late diastolic A wave, atrial active work index, and increased V waves. Consistently, in Aldo rats, sarcomere shortening and the amplitude of electrically evoked global Ca2+transients were substantially reduced. Sarcoplasmic reticulum-Ca2+content and fractional Ca2+release were decreased, substantiated by a reduced sarcoplasmic reticulum calcium ATPase activity, resulting from a reduced CAMKII-evoked phosphorylation of phospholamban. Hyperaldosteronism induced atrial systolic and diastolic dysfunction, while atrial size and left ventricular hemodynamics, including filling pressures, were unaffected in rats. The described model suggests a direct causal link between hyperaldosteronism and decreased atrial contractility and diastolic compliance.
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; Klinik für Innere Medizin II, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitäres Herzzentrum Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany; jan-christian.reil@uksh.de.
Jan-Christian
JC
Reil
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Marcus
M
Tauchnitz
Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, Homburg/Saar, Germany.
Qinghai
Q
Tian
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Mathias
M
Hohl
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Dominik
D
Linz
Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, Homburg/Saar, Germany.
Martin
M
Oberhofer
Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, Homburg/Saar, Germany.
Lars
L
Kaestner
Klinik für Innere Medizin I, Kardiologie, Klinikum Oldenburg, Oldenburg, Germany.
Gert-Hinrich
GH
Reil
Klinik für Innere Medizin II, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitäres Herzzentrum Lübeck, Universitätsklinikum Schleswig-Holstein, Lübeck, Germany.
Holger
H
Thiele
Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands; and.
Paul
P
Steendijk
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.
Michael
M
Böhm
Klinik für Innere Medizin III (Kardiologie, Angiologie, Internistische Intensivmedizin), Universitätsklinikum des Saarlandes, Homburg/Saar, Germany; Klinikum Traunstein, Sektion Rhythmologie, Traunstein, Germany.
Hans-Ruprecht
HR
Neuberger
Institute for Molecular Cell Biology and Research Centre for Molecular Imaging and Screening, Saarland University, Homburg/Saar, Germany.
Peter
P
Lipp
D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D003971:Diastole; D006325:Heart Atria / Q000187:drug effects*; D006439:Hemodynamics / Q000187:drug effects*; D006929:Hyperaldosteronism / Q000503:physiopathology; D009200:Myocardial Contraction / Q000187:drug effects*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D000450:Aldosterone; D002118:Calcium
aldosterone; atrial function; hemodynamics