P265	Effects of serotonin on ischaemic and ischaemic and reperfused middle cerebral arteries of the rat, in vitro.
A.Kovács, L.G.Hársing, G.Szénási
EGIS Pharmaceuticals Ltd., Division of Preclinical Research, Budapest, HU.

Rat middle cerebral arteries (MCA) receive serotonergic innervation from the dorsal raphe nucleus. Moreover, 5-HT may be released into the local circulation under pathophysiological circumstances (platelet aggregation and haemorrhage). Thus, 5-HT is an important vasoactive agent that can play a role in the regulation of cerebral circulation. The aim of our study was to evaluate if ischaemia (1-hour occlusion of the right MCA using the intravascular filament technique) without reperfusion (ISC) or ischaemia followed by a 24-hour reperfusion (ISCR) influences or not the vascular sensitivity (EC50) and the maximum contraction (Emax) to 5-HT and also (Emax) to a solution containing 120 mM K+ (KS). Therefore, the contractile effects of these agents were compared in right and left MCA of rats, in vitro. Ring preparations (2 mm) were mounted horizontally using two tungsten wires (40 μM in diameter) in an organ chamber (Myo-01, EXPERIMETRIA) filled with 6 ml Krebs solution, maintained at 37 C° and bubbled with a mixture of 95 % O2 and 5 % CO2. Two groups of rats were tested simultaneously, control rats and rats with ISCR, as well as sham operated rats and rats with ISC. Sensitivity of MCA to 5-HT decreased significantly on both sides after ischaemia without reperfusion. On the contrary, contractile potency of 5-HT did not differ in MCA obtained from both sides in control and ISCR rats, as EC50 values were similar. However, Emax value evoked by 5-HT in the right MCA after ISCR was depressed compared to the right and left MCA from control animals and also to the left MCA from ISCR rats (62.5±8.1 mg vs. 99.1±5.2, 100.1±5.8 and 100.4±9.2 mg; p<0.01). Thus, contractions to 5-HT were attenuated only on the occluded side after ISCR. Emax values evoked by KS were significantly lower on both sides after ISC and ISCR, compared to that of control and sham operated rats, demonstrating a general reduction in the vasoconstrictor capacity after ischaemia. These findings indicate that ischaemia followed by 24-hour reperfusion selectively reduces the maximum vasoconstriction to 5-HT, but ischaemia and ischaemia followed by reperfusion causes a similar reduction in vasoconstriction to high K+ solution on both the affected and contralateral middle cerebral artery of the rat, in vitro.

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