Alterations of cardiac contractile function are related to changes in membrane calcium transport in spontaneously hypertensive rats

Objective : Transport activities of cardiac sodium-calcium exchange and sarcoplasmic reticulum calcium ATPase were measured biochemically in spontaneously hypertensive rats (SHR) with hypertrophied myocardium and in normotensive Wistar-Kyoto (WKY) rats and it was tested whether possible differences have consequences for the contractile properties of papillary muscle. Methods : Sarcolemmal sodium-dependent calcium transport via sodium-calcium exchange and oxalate-supported sarcoplasmic reticulum calcium uptake were measured in left ventricular membranes of 22-week-old rats. Postextrastimulatory potentiated contractions, postrest potentiated contractions, the twitch-to-twitch decay of those potentiations and the response to increasing stimulation frequency of left ventricular papillary muscles were analysed. Results : Compared with WKY rats we found in SHR : a significant increase in sodium-calcium exchange (65%) and in sarcoplasmic reticulum calcium uptake (24%) ; a steeper twitch-to-twitch decay in postextrastimulatory potentiated contractions and postrest potentiated contractions, suggesting a lower calcium fraction recirculating between myofilaments and sarcoplasmic reticulum and, consequently, a relatively higher calcium efflux via sodium-calcium exchange ; a stronger rest-dependent decrease in recirculating calcium fraction in postrest potentiated contractions accompanied by accelerated relaxation, suggesting an increasing driving force for calcium extrusion via sodium-calcium exchange, probably caused by decreasing intracellular sodium during rest ; a greater transient decrease in peak force of subsequent twitches after postrest potentiated contractions below pre-interventional level, indicating higher cellular calcium loss ; and a smaller negative inotropic effect in response to doubling of stimulation rate as a manoeuvre to increase the intracellular sodium level. Conclusion : In SHR, the contractile properties suggest an increased contribution of sodium-calcium exchange to cellular calcium removal, which is strongly supported by the enhanced sodium-calcium exchange activity in cardiac membrane vesicles.