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Hoe 694, a new Na+/H + exchange inhibitor and its effects in cardiac ischaemia
Author(s) -
Scholz W.,
Albus U.,
Lang H.J.,
Linz W.,
Martorana P.A.,
Englert H.C.,
Schölkens B.A.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13607.x
Subject(s) - lactate dehydrogenase , medicine , ventricular fibrillation , creatine , ventricular pressure , ischemia , creatine kinase , amiloride , endocrinology , chemistry , pharmacology , sodium , blood pressure , biochemistry , enzyme , organic chemistry
1 The benzoylguanidine derivative Hoe 694 ((3‐methylsulphonyl‐4‐piperidino‐benzoyl) guanidine methanesulphonate) was characterized as an inhibitor of Na + /H + exchange in rabbit erythrocytes, rat platelets and bovine endothelial cells. The potency of the compound was slightly lower or comparable to ethylisopropyl amiloride (EIPA). 2 To investigate a possible cardioprotective role of the Na + /H + exchange inhibitor Hoe 694, rat isolated working hearts were subjected to ischaemia and reperfusion. In these experiments all untreated hearts suffered ventricular fibrillation on reperfusion. Addition of 10 −7 m Hoe 694 to the perfusate almost abolished reperfusion arrhythmias in the rat isolated working hearts. 3 Hoe 694 reduced the release of lactate dehydrogenase (LDH) and creatine kinase (CK), which are indicators of cellular damage during ischaemia, into the venous effluent of the hearts by 60% and 54%, respectively. 4 The tissue content of glycogen at the end of the experiments was increased by 60% and the high energy phosphates ATP and creatine phosphate were increased by 240% and 270% respectively in the treated hearts as compared to control hearts. 5 Antiischaemic effects of the Na + /H + exchange inhibitor, Hoe 694, were investigated in a second experiment in anaesthetized rats undergoing coronary artery ligation. In these animals, pretreatment with Hoe 694 caused a dose‐dependent reduction of ventricular premature beats and ventricular tachycardia as well as a complete suppression of ventricular fibrillation down to doses of 0.1 mg kg −1 , i.v. Blood pressure and heart rate remained unchanged. 6 We conclude that the new Na + /H + exchange inhibitor, Hoe 694, shows cardioprotective and antiarrhythmic effects in ischaemia and reperfusion in rat isolated hearts and in anaesthetized rats. In view of the role which Na + /H + exchange seems to play in the pathophysiology of cardiac ischaemia these effects could probably be attributed to Na + /H + exchange inhibition.