1. Alterations in intracellular Ca(2+) homeostasis have frequently been implicated as underlying the contractile dysfunction of failing hearts. Contraction in cardiac muscle is due to a balance between sarcolemmal (SL) and sarcoplasmic reticulum (SR) Ca(2+) transport, which has been studied in single cells and small tissue samples. However, many studies have not used physiological temperatures and pacing rates, and this could be problematic given different temperature dependencies and kinetics for transport processes. 2. Spontaneously-hypertensive rats (SHR) and their age-matched Wistar Kyoto controls (WKY) provide an animal model of hypertensive failure with many features in common to heart failure in humans. Steady-state measurements of Ca(2+) and force showed that peak stress was reduced in trabeculae from failing SHR hearts in comparison to WKY, although the Ca(2+) transients were bigger and decayed more slowly. 3. Dynamic Ca(2+) cycling was investigated by determining the recirculation fraction (RF) of activator Ca(2+) through the SR between beats during recovery from experimental protocols that potentiated twitch force. No difference in RF between rat strains was found, although the RF was dependent on the potentiation protocol used. 4. Superfusion with 10 mmol/L caffeine and 0 mmol/L [Ca(2+) ](o) was used to measure SL Ca(2+) extrusion. The caffeine-induced [Ca(2+) ](i) transient decayed more slowly in SHR trabeculae, suggesting that SL Ca(2+) extrusion was slower in SHR. 5. An ultrastructural immunohistochemical analysis of left ventricular free wall sections using confocal microscopy showed that t-tubule organization was disrupted in myocytes from SHR, with reduced labelling of the SR Ca(2+) -ATPase and Na(+) -Ca(2+) exchanger in comparison to WKY, with the latter possibly related to a lower fraction of t-tubules per unit cell volume. 6. We suggest that although Ca(2+) transport is altered in the progression to heart failure, force development is not limited by the amplitude of the Ca(2+) transient. Despite slower SR Ca(2+) transport, the recirculation fraction and dynamic response to a change of inotropic state minimally altered changes in the SHR model because there was a similar slowing in Ca(2+) extrusion across the surface membrane.
|Pages (from-to)||711 - 716|
|Number of pages||6|
|Journal||Clinical and Experimental Pharmacology and Physiology|
|Publication status||Published - Oct 2011|
Bibliographical notePublisher: Blackwell Publishing Asia Pty Ltd
Ward, M-L., Crossman, D. J., & Cannell, MB. (2011). Mechanisms of reduced contractility in an animal model of hypertensive heart failure. Clinical and Experimental Pharmacology and Physiology, 38, 711 - 716. https://doi.org/10.1111/j.1440-1681.2011.05563.x