INDUCTION OF EXPRESSION OF THE SODIUM-HYDROGEN EXCHANGER IN RAT MYOCARDIUM

Objective: The aim was to examine the regulation of the cardiac Na+/H exchanger NHE-1 isoform mRNA in response to ischaemia and acidosis in the mammalian myocardium. Methods: Male Sprague Dawley rat hearts wer e perfused in a non-circulated retrograde fashion according to the Lan gendorff method. Hearts were perfused for 3 h at flow rates of either 10 ml.min(-1) (control), or 3, 1, or 0 ml.min(-1) (ischaemia) followed by 5 min of reperfusion. Hearts were immediately frozen in liquid Nz, and stored at -80 degrees C until ready for RNA isolation. Northern b lot analysis was used to examine expression of the NHE-1 isoform of th e Na+H+ exchanger message in these isolated perfosued hearts. Activity of the Na+/H+ exchanger was assessed in primary cultures of neonatal rat myocytes under either control conditions or after treatment with c hronic, low external pH. Results: A decrease in developed tension and an increase in resting tension was observed which was dependent upon t he severity of the ischaemic episode. Low flow ischaemia of 3 ml.min(- 1) caused increased Na+/H+ exchanger message levels, while perfusion a t more reduced flow rates eliminated the increase. Treatment of primar y cultures of isolated myocytes with low external pH resulted in incre ased ability to recover from an acute acid load. Conclusions: Low flow ischaemia can increase the Na+/H+ exchanger message in the intact mam malian myocardium. More severe ischaemia prevents the increase, sugges ting that severely damaged tissue may not be capable of the ischaemic response. Primary cultures of isolated myocytes can respond to chronic low external pH by increasing Na+/H+ exchanger activity.