Hyperaldosteronism induces left atrial systolic and diastolic dysfunction.

Abstract

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.

• Authors: Jan-Christian Reil, Marcus Tauchnitz, Qinghai Tian, Mathias Hohl, Dominik Linz, Martin Oberhofer, Lars Kaestner, Gert-Hinrich Reil, Holger Thiele, Paul Steendijk, Michael Böhm, Hans-Ruprecht Neuberger, Peter Lipp
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 311 Issue 4 Pg. H1014-H1023 (10 01 2016) ISSN: 1522-1539 [Electronic] United States
• PMID: 27614224 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 the American Physiological Society.

Chemical References

• Aldosterone
• Calcium

Topics

• Aldosterone (pharmacology)
• Animals
• Atrial Function, Left (drug effects)
• Calcium (metabolism)
• Diastole
• Heart Atria (drug effects)
• Hemodynamics (drug effects)
• Hyperaldosteronism (physiopathology)
• Myocardial Contraction (drug effects)
• Pressure
• Rats
• Rats, Sprague-Dawley
• Sarcoplasmic Reticulum (drug effects, metabolism)
• Systole
• Ventricular Function, Left (drug effects)
• Ventricular Pressure (drug effects)