ИСТИНА

Nitric oxide (NO)-dependent relaxation involves two global mechanisms: dependent and not-dependent on soluble guanylate cyclase (sGC). Contribution of these mechanisms to the development of the pulmonary arterial hypertension, which often is an integral part of many types of congenital heart diseases, is not completely investigated. Objective: We estimated the contribution of the sGC-dependent mechanism and of the ATP-sensitive K+ channels to the NO-dependent relaxation in lung vessels in the model of congenital heart disease with left-to-right blood shunt. Design and method: Wistar male rats were used at the age of 1 month. An operation making a shunt between carotid artery and jugular vein was performed. One month later we carried out an experiment on isolated second-order intrapulmonary artery. We measured the response to NO donor (sodium nitroprusside with the concentration varying from 10-11 to 10-7 М with the step of one order of magnitude). The level of suppression by blocker of sGC (ODQ, 1мкМ) and ATP-sensitive K+ channels antagonist (glibenclamide, 5мкМ) of NO-dependent relaxation was estimated. The study of the dilatation reactions was against the background of the vasoconstriction reaction for serotonin (5х10-6 М in Krebs-Henseleit solution). Results and conclusions: We obtained the decrease of the response to sodium nitroprusside in both cases with the blocker of sGC and with ATP-sensitive K+ channels antagonist. The level of the suppression by ODQ was significantly less in the group with the shunt than in the pseudo-operated rats. Therefore, the contribution of sGC-dependent mechanism decreases in the model of congenital heart diseases. The suppression of relaxation by ATP-sensitive K+ channels antagonist were stronger pronounced, than by the blocker of sGC. The possible reason is that in the condition of the congenital heart disease with left-to-right blood shunt, associated with disturbances of sGC function, NO-dependent relaxation in lung vessels is realized mostly by ATP-sensitive K+ channels on the membrane of the smooth muscle cells.