Translational Medicine II. (Poster discussion will take place in the Aula during the Coffee Break)
Dr. Balint, Banyai
Semmelweis University Department of Physiology
06705783752
banyai.balint@gmail.com
Delta9-tetrahydrocannabinol conserves cardiovascular functions in a rat model of endotoxemia: involvement of endothelial molecular mechanisms and oxidative-nitrative stress.
Bálint Bányai1; Johnny Johnsen1; Eszter M. Horváth1; Rita Benkő1
1: Semmelweis University Department of Physiology Budapest
Poszter
Translational Medicine II. (Poster discussion will take place in the Aula during the Coffee Break)
Hungarian
Theoretical and Translational Medicine
Endotoxemia is accompanied by severe cardiovascular dysfunction, in which inflammatory processes and oxidative-nitrative stress play important roles. Recently, several research groups described that inflammatory parameters in endotoxic animal models were altered to a favorable direction as a response to the activation of cannabinoid receptors 1 and 2. Our aim was to examine the effect of cannabinoid treatment on the cardiovascular system in endotoxemia.
Male Wistar rats were treated with LPS (5 mg/kg i.v.) to induce endotoxemia. A group of animals received additional delta9-tetrahydrocannabinol THC (10 mg/kg i.p.). 24 hours later we examined their cardiac function by echocardiography and via intra ventricular pressure monitoring. Endothelium-dependent, acetylcholine induced relaxation of the thoracic aorta rings was measured by wire-myography. To evaluate the molecular mechanism, endothelial NOS, COX-2, cGMP, the oxidative stress marker 4-hydroxynonenal (HNE), the nitrative stress marker 3-nitrotyrosine (NT), and poly(ADP-ribose) polymer (PAR) was labelled by immunoshistochemistry.
A decrease in the end-systolic and the end-diastolic ventricular volumes with sustained ejection fraction and fractional shortening was found in the LPS group, which was not observed in LPS+THC animals. Endothelium-dependent relaxation worsened in the LPS group, however no significant endothelial dysfunction was present in the LPS+THC group compared to controls. cGMP staining density was reduced in both LPS treated groups independent from THC treatment, although eNOS labeling was only reduced in the LPS+THC treated animals. COX-2 staining density was only reduced in the LPS+THC treated group. Tissue oxidative (HNE) and nitrative (NT) stress increased after LPS treatment, which was reversed by THC co-treatment. The significant increase in PAR-ylation after LPS was prevented by THC.
Based on our results, we hypothesize that the reduced diastolic filling in the LPS group is a consequence of vascular dysfunction, which was prevented by THC. The mechanism of action of THC is not based on its local effect on aortic NO homeostasis. The reduced oxidative-nitrative stress and the reduced detectability of COX-2 suggest the activation of an anti-inflammatory pathway.
Semmelweis University, Doctoral School of Theoretical and Translational Medicine
Rita Benkő
I give consent to the publication of my abstract on the website of the congress.
Szabad
elfogadva
poszter
nem rendelkezett róla
6054
13:20
13:25
Bálint Bányai1; Johnny Johnsen1; Eszter M. Horváth1; Rita Benkő1
1: Semmelweis University Department of Physiology Budapest