engleski

The mechanisms of vascular reactivity to ACh and serotonin are modulated by hyperbaric oxygen treatment in cerebral resistance arteries of diabetic rats

Introduction Functional recovery of patients after ischemic stroke (1) and myocardial infarction (2) are better if they are treated with hyperbaric oxygen therapy. The aim of this study was to identify mechanisms whereby HBOT influences vascular reactivity to acetylcholine (ACh) and serotonin in isolated, cannulated and perfused middle cerebral arteries (MCA). Methods Sprague-Dawley (SD) male rats (12 weeks old at the time of experiments, duration of DM 6 weeks) were divided in 4 groups: control group ; streptozocin-induced (60 mg/kg i.p.) diabetic group (DM) ; diabetic group that underwent HBOT (DM+HBOT) and control group that underwent HBOT (control +HBOT). . Rats were exposed to HBOT at 2, 0 ATM in duration of 120 min for 4 consecutive days before experiments. Statistical analyses were performed with one way ANOVA, p<0.05 as significant. Results Vasodilation in response to ACh (10-6M) was impaired in MCA of DM rats compared to control rats. HBOT restored ACh-induced dilation in DM-HBOT rats. Inhibition of nitric-oxide synthase (NOS) with L-NMMA (10-5M) eliminated ACh-induced dilation in control and DM groups of rats, however ACh vasodilation tended to be preserved in DM+HBOT and control +HBOT group. After inhibition of epoxygenases with clotrimazol (10-5M), vasodilation to Ach (10-6M) was preserved in all groups except DM group of rats. Response to Serotonin (Ser 10-6M) was eliminated after inhibition of cyclooxygenase (COX) with indometacin (10-5M), in control and DM group, but Ser- induced vasoconstriction was preserved in DM+HBOT and control +HBOT rat groups. Conclusion, our results suggest that vasodilation in response to ACh is mediated by NO in control group, but restored vasodilation in DM-HBOT rats is possibly mediated with some vasodilator metabolite of CYP450 epoxygenases (such as EETs). Additionally, preserved constriction to Ser in both HBOT-treated groups suggests the release of vasoconstrictor metabolites other than of COX1, 2 origins. Acknowledgement: supported by Croatian Ministry of Science, Education and Sports‟s grant #219-2160133-2034. 1. Yin W, Badr AE, Mychaskiw G, Zhang JH. Down regulation of COX-2 is involved in hyperbaric oxygen treatment in a rat transient focal cerebral ischemia model. Brain Research2002 ; 926:165-171. 2. Camporesi EM. Hypertbaric oxygen therapy: Committee report of the Undersea and Hyperbaric Medical Socety. Kensington, MD, 1996 p74.

hyperbaric oxygen therapy; rats; acetylcholine; serotonin diabetes mellitus

nije evidentirano