Роль индуцибельной NO-синтазы в развитии церебральной гиперемии после ишемии/реперфузии

Abstract

This work was aimed to study the iNOS role in the pial arterial vascular tone regulation and tissue perfusion in the post-ischemic time in the first 7 days after ischemia/reperfusion (I/R). Ischemia was induced in anesthetized Wistar rats (n=33) by clamping of both common carotid arteries for 12 min with simultaneous controlled hypotension to 45±3 mm Hg. The diameter changes of pial arteries and arterioles were visialised using in-vivo video microscopy. The responses response to selective iNOS inhibitor aminoguanidine (AG) and non-selective inhibitor of NO-synthases by L-NAME were studied. At the same time tissue perfusion (P) and hematocrit were determined in the same animals. 5 different groups of rats were studeid: intact (control), and 1 hour, 1, 3, or 7 days after ischemia. The maximal (1.6 times) increase in P was observed 1 hour after I/P, and after 1 day it returned to the control level. The tissue hematocrit was increased at 1 hour after the I/R, and peaked on the 3rd day (by 40%). After 7 days the hematocrit remained about 20% higher than in control. In control rats, L-NAME reduced the vessels diameter by 10-14% on average, and AG did not lead to significant changes in the diameter. The AG effect on the vessels was observed only in the time period from 1 to 3 days after I/R. At this time, the effect of AG was similar to that of L-NAME. At 7th day, the pial artery reactions to AG and L-NAME decreased to the control levels. We conclude that the NO-mediated dilation of the pial arteries caused by the iNOS expression plays a prominent role in the cerebral tissue hyperemia in the first 7 days of the post-ischemic period.