Comparison of the protective actions of Na+/H+ and Na+/Ca2+ exchange inhibitors in ischemic/reperfused rat hearts

Autor: Mitsuyoshi Ninomiya, Mitsuo Ishii, Yoshinori Kitano, Kazumi Iwaki, Hiroko Tachibana
Rok vydání: 1999
Předmět:
Zdroj: Drug Development Research. 48:160-170
ISSN: 1098-2299
0272-4391
DOI: 10.1002/(sici)1098-2299(199912)48:4<160::aid-ddr3>3.0.co;2-c
Popis: The protective effects of the Na + /H + exchange inhibitors amiloride, EIPA (5-(N-ethyl-N-sopropyl)-amiloride), and HOE 694 (3-methylsulfonyl-4-(1-piperidino) benzoyl-guanidine) and the Na + / Ca 2+ exchange inhibitor, DCB (3,4-Dichlorobenzamil) on ischemia (30 min) / reperfusion (30 min) injury were studied using Langendorff perfused rat hearts. EIPA and HOE 694 given before ischemia protected the heart during reperfusion from mechanical and metabolic disturbances. A weak protective effect was observed with amiloride, but not with DCB. The cardioprotective efficacies of these compounds correlated with their potencies as Na + /H + exchange inhibitors as assessed by the NH 4 Cl prepulse method. None of the inhibitors was effective when given at reperfusion. EIPA and HOE 694 decreased myocardial rigidity as assessed by the resting tension (RT) which elevated during reperfusion. EIPA led to a more marked attenuation of RT elevation during reperfusion rather than ischemia, whereas diltiazem, a Ca 2+ channel blocker, suppressed RT elevation during ischemia but did not cause a further attenuation of RT during reperfusion. Treatment with EIPA as well as diltiazem before ischemia showed a direct negative chronotropic effect. Cardioprotective effects were also observed with diltiazem. These results suggest that Na + /H + exchange plays a more important role in ischemia-reperfusion-induced myocardial injury than does Na + /Ca 2+ exchange. The cardioprotective effects of EIPA appear to be produced by Ca 2+ channel blockade during ischemia and by Na + /H + exchange inhibition during reperfusion.
Databáze: OpenAIRE
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