BLOCKERS OF AQUAPORIN CHANNELS AND CARBON MONOXIDE INFLUENCE THE MYOCARDIUM IN CONDITIONS OF ISCHEMIA-REPERFUSION
Abstract
Functioning of the cardiovascular system is provided by ion and aquaporin channels. Their disfunction cause damage to the whole body, reducing working efficiency and quality of life. Ischemia is the main factor affecting damage to the cardiovascular system. Myocardial reperfusion is often accompanied by negative processes, interstitial and cellular edema occurs. Water transport in the tissues of the cardiovascular system is provided by special channels called aquaporins. They also transport glycerol, urea and ammonia. The possibility of controlled exposure to these channels is an important target for the development of drugs that reduce ischemia-reperfusion injury. Carbon monoxide and anticonvulsants (lamotrigine and valproates) deserve special attention as blockers of aquaporin channels. The studies were performed on laboratory mice, which were divided into 5 groups. The first
group was control; mice of the second-fourth groups were injected through a probe with phenytoin, lamotrigine, and topiramate, respectively. In the fifth group, a perfusion solution was passed through the isolated heart during perfusion, which was saturated with CO for 30 min. To study coronary flow, metabolic changes and individual indicators of electrical activity, we used retrograde perfusion technique of isolated heart on which ischemia and reperfusion were simulated. Phenytoin, lamotrigine, and CO were found to have vasodilator properties, however topiramate had a vasoconstrictor effect. Lamotrigine reduced glucose absorption during perfusion, phenytoin and topiramate – at the end of reperfusion, and CO – during reperfusion. Са2+ depositing was found in the group that received phenytoin. In the group with lamotrigine and topiramate, the depositing was at the beginning of reperfusion. The use of perfusion solution with CO conditioned Са2+ accumulation only at the end of reperfusion. Increased creatinine production was observed only in the groups that received phenytoin and topiramate. Aspartate aminotransferase levels were increased only in the group with lamotrigine at the time before ischemia. Anticonvulsants and CO, during perfusion, decreased the amplitude of the R waveform, whereas during ischemia, on the contrary, there was an increase in voltage. R-R interval shortening occurred only in the group with phenytoin. Lamotrigine and topiramate lengthened the interval, CO shortened the interval during reperfusion. Thus, the effects on aquaporin channels led to changes in coronary flow, glucose metabolism, and myocardial calcium depositing, and also the extent of myocardial damage during ischemia-reperfusion was reduced.
Key words: aquaporins, valproates, gas-transmitter, myo
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