ALTERATIONS OF CARDIAC CONTRACTILE FUNCTION ARE RELATED TO CHANGES INMEMBRANE 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 an d in normotensive Wistar-Kyoto (WKY) rats and it was tested whether po ssible differences have consequences for the contractile properties of papillary muscle. Methods: Sarcolemmal sodium-dependent calcium trans port via sodium-calcium exchange and oxalate-supported sarcoplasmic re ticulum calcium uptake were measured in left ventricular membranes of 22-week-old rats. Postextrastimulatory potentiated contractions, postr est potentiated contractions, the twitch-to-twitch decay of those pote ntiations and the response to increasing stimulation frequency of left ventricular papillary muscles were analysed. Results: Compared with W KY rats we found in SHR: a significant increase in sodium-calcium exch ange (65%) and in sarcoplasmic reticulum calcium uptake (24%); a steep er twitch-to-twitch decay in postextrastimulatory potentiated contract ions and postrest potentiated contractions, suggesting a lower calcium fraction recirculating between myofilaments and sarcoplasmic reticulu m and, consequently, a relatively higher calcium efflux via sodium-cal cium exchange; a stronger rest-dependent decrease in recirculating cal cium fraction in postrest potentiated contractions accompanied by acce lerated 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 los s; and a smaller negative inotropic effect in response to doubling of stimulation rate as a manoeuvre to increase the intracellular sodium l evel. Conclusion: In SHR, the contractile properties suggest an increa sed contribution of sodium-calcium exchange to cellular calcium remova l, which is strongly supported by the enhanced sodium-calcium exchange activity in cardiac membrane vesicles.