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Objective: Placement of a soft silicone collar around the carotid arteries of rabbits induces intimal thickening which is considered as one of the crucial steps in the development of atherosclerosis. In this study we aimed to investigate vWF expression levels on days 7 and 14 after collar placement. Methods: A soft inert silicon collar was placed around the left carotid artery for 7 and 14 days. vWF expression was investigated by quantitave RT-PCR. In each artery (collar or sham) cross-sectional areas of intima, media were measured and intima/ media ratio was calculated. Results: Intimal thickening was more pronounced on day 14 compared to day 7. However the collar caused increase in vWF expression which was found to be at the same level on days 7 and 14. Conclusion: Our findings emphasize the importance of vWF in collar-induced intimal thickening. [ABSTRACT FROM AUTHOR]

Introduction: Hydrogen sulfide (H2S), known as a third gasotransmitter, is a signaling molecule that plays a regulatory role in physiological and pathophysiological processes. Decreased H2S levels were reported in inflammatory respiratory diseases such as asthma, chronic obstructive pulmonary disease, and pulmonary hypertension. H2S donors or drugs that increase H2S have emerged as novel treatments for inflammatory respiratory diseases. We previously showed that resveratrol (RVT) causes vascular relaxation and antioxidant effects by inducing H2S production. In the current study, we synthesized a new molecule Cpd2, as an RVT analog. We examined the effect of Cpd2 and its precursor chalcone compound (Cpd1) on H2S formation under both healthy and oxidative stress conditions in the lung, as well as vascular relaxation in the aorta. Methods: Cpd2 synthesized from Cpd1 with microwaved in basic conditions. H2S formation was measured by H2S biosensor in the mice lungs under both healthy and pyrogallol-induced oxidative stress conditions in the presence/absence of H2S synthesis inhibitor aminooxyacetic acid (AOAA). The effect of compounds on vascular tonus is investigated in mice aorta by DMT myograph. Results: RVT and Cpd2 significantly increased l-cysteine (l-cys) induced-H2S formation in the lung homogenates of healthy mice, but Cpd1 did not. Superoxide anion generator pyrogallol caused a decrease in H2S levels in mice lungs and Cpd2 restored it. Inhibition of Cpd2-induced H2S formation by AOAA confirmed that Cpd2 increases endogenous H2S formation in both healthy and oxidative stress conditions. Furthermore, we found that both Cpd1 and Cpd2 (10−8–10−4 M) caused vascular relaxation in mice aorta. Discussion and Conclusion: We found that Cpd2, a newly synthesized RVT analog, is an H2S-inducing molecule and vasorelaxant similar to RVT. Since H2S has antioxidant and anti-inflammatory effects, Cpd2 has a potential for the treatment of respiratory diseases where oxidative stress and decreased H2S levels are present. [ABSTRACT FROM AUTHOR]

It has been extensively demonstrated that hydrogen sulfyde (H 2 S) is implicated is several physiological and pathological conditions (J Mol Med, 2012 Mar;90(3):255–63). In particular, it has been shown that H 2 S causes relaxation in human penile tissues (Proc Natl Acad Sci USA, 2009 Mar 17;106(11):4513–8) and inhibits phosphodiesterase (PDE) activity in vessels (ATVB 2010, Oct;30(10):1998–2004). Beside sildenafil increases H 2 S generation in human bladder (Eur Urol. 2012 Dec;62(6):1174–80) and tadalafil in myocardial tissues (Circulation 2009, 120:S31-S36). Therefore, our aim was to demonstrate the link between H 2 S and PDE-5 in mice corpus cavernosum tissues. Thus, we investigated the effects of sildenafil (10 μM, 0.5 h); PDE-5 inhibitor, on H 2 S production as well as the H 2 S -induced relaxations in mice penile tissues. Penile tissues from CD1 mouse corpus cavernosum (MCC) were used. Functional studies were performed by myograph in Krebs solution. Western blot analysis was performed in order to evaluate CBS and CSE expression and methylene blue assay for measurement of H 2 S levels. In order to investigate functional significance of H 2 S on sildenafil-induced augmentation of endothelial relaxation in MCC the sildenafil effect was evaluated on acetylcholine (ACh; 10–9-10–4 M), L-cysteine (10–6-10–3 M) and NaHS-induced relaxations in presence or not of CSE enzyme inhibitor PPG (10 μM, 0.5 h). In order to achieve this issue the H 2 S production in MCC tissues was also evaluated by incubating the penile tissue with sildenafil in presence or absence of the CSE inhibitor PPG (10 μM, 0.5 h) Both CBS and CSE were expressed in MCC and the enzymes efficiently converted L-cysteine into H 2 S. Further we showed that sildenafil caused a significant increase in H 2 S production and this augmentation was reversed by CSE inhibition. We found that sildenafil induced an increase in both ACh and L-cysteine–induced relaxations and these augmentations reversed by CSE inhibitor PPG in MCC pre-contracted with phenylephrine (3.10–5 M). Beside sildenafil did not significantly increase the NaHS –induced relaxations. Therefore we suggest that both gaseous transmitters NO and H 2 S affect sildenafil action. In particular our results demonstrate that sildenafil effect is partially mediated by H 2 S pathway. Thus, H 2 S signaling may represent a new mechanism involved in the effect of sildenafil on erectile dysfunction. [ABSTRACT FROM AUTHOR]