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Objective. Patients and medical professionals have a common misconception that cardiovascular diseases (CVD) predominantly affect men, which can lead to less prescribing of cardiovascular drugs to women. This study examined whether there were sex differences in the administration of cardiovascular (CV) drugs in patients admitted to the intensive care unit of the Internal Medicine Clinic of Foča University Hospital (ICFUH).Materials and Methods. The study comprised 332 patients hospitalized at the ICFUH from January 1st to June 30th, 2019. The following data on leading CVD and risks related to CV drug administration were collected: age, hyperlipidemia (HLD), diabetes mellitus (DM), chronic kidney disease (CKD), liver disease (LD), heart failure (HF), hypertension (HTN), myocardial infarction (MI), and stroke (S). The amount of the CV drugs of interest (statins, antiplatelet drugs, calcium channel blockers, ACE inhibitors, beta blockers, diuretics) administered during hospitalization was expressed as the Defined Daily Dose (DDD)/100 bed-days (BD) for patients of both sexes separately.Results. During hospitalization in the intensive care unit of ICFUH, female patients were less likely to be treated with statins than male patients (30.1 vs. 57.5 DDD/100 BD, PConclusion. Our study indicates that there were sex differences in CV drug administration in ICFUH. Presuming that drugs used during hospitalization were at least partially a continuation of the previous therapy prescribed by the family doctor, it is possible that such differences exist in primary care.

Background. Pentoxifylline, used for treating peripheral vascular deceases is a derivate of methylxanthines. One way of pentoxifylline action is by causing vasodilatation of blood vessels. In this study, the effect of increasing concentrations of pentoxifylline, in the presence of potassium channel antagonist, on contractility of isolated rat uterus was examined. Methods . Uteruses were isolated from virgin Wistar rats (180-220 g) and suspended in an isolated organ bath chamber containing De Jalon's solution and aerated with 95% O 2 and 5% CO 2 . Temperature was maintained at 37oC. Isometric contractions were recorded using an isometric force transducer (Ugo Basile). The preload of the preparation was about 1g. Uteri were allowed to contract spontaneously or in the presence of Ca 2+ (0.018 and 0.36 mM ) and acetylcholine and treated with pentoxifylline. Results. Pentoxifylline caused concentration-dependent inhibition of spontaneous rhythmic uterine activity and uterine activity caused by calcium Ca 2+ (0.018 mM and 0,36 mM). We showed that the inhibitory effect of pentoxifylline depends on type of muscle contraction activation, and that it is significantly stronger in spontaneous rhythmic activity and contraction of isolated rat uterus induced by Ca 2+ . The relaxing effect of pentoxifylline depends on calcium concentration of in the medium. Pentoxifylline exerted the weakest relaxant effects on contractions induced by acetylcholine (Ach). As opposed to methylene blue, tetraethylammonium, and 4-aminopyridine, glibenclamide did not antagonize the relaxing effect of pentoxifylline on the isolated rat uterus. Conclusion. Results obtained suggest that the mechanism of action of pentoxifylline did not lead to the opening of K ATP channels. However, the opening of BKCa and of voltage dependent Ca 2+ channel had some significance, but to varying degrees, in the mechanism of the relaxing effect of pentoxifylline on spontaneous rhythmic activity and contraction of the isolated rat uterus induced by calcium. Our results are additional confirmation of the dominance of the NO/cGMP signaling pathway in the mechanism of the relaxing effect of pentoxifylline (because the presence of methylene blue significantly antagonizes its effect) in relation to the opening of potassium channels, especially K ATP channels. These results indicate that pentoxifylline could be a potential tocolytic drug. Keywords: pentoxifylline, rat uterus, potassium channel blockers, glibenclamide (GLB), tetraethylammonium (TEA), 4-aminopyridine (4-AP ), methylene blue (MB) Running title: Potassium Channels in Action of Pentoxifylline

The present paper describes environmental and seasonal-related chemical composition variations, vasorelaxant and angiotensin I-converting enzyme (ACE) activities of essential oil from aerial parts of Seseli pallasii BESSER. The composition was analyzed by GC and GC/MS. Monoterpenes were found to be the most abundant chemical class with alpha-pinene (42.7 - 48.2%) as the most prevalent component. Seseli pallasi essential oil relaxed isolated endothelium-intact mesenteric arteries rings precontracted with phenylephrine with IC50 = 3.10 nl/ml (IC50 = 2.70 mu g/ml). Also, S. pallasii essential oil was found to exhibit a dose-dependent ACE inhibitory activity with an IC50 value of 0.33 mg/ml. In silico evaluation of ACE inhibitory activity of the individual components showed that spathulenol exhibited the best binding affinity with ACE, and the lowest binding energy of -7.5 kcal/mol. The results suggested that combination of vasorelaxing and ACE inhibitory effects of the analyzed S. pallasii essential oil might have the potential therapeutic significance in hypertension.