The renin-angiotensin-aldosterone system (RAAS) is more complex than it was originally regarded. According to the current subject knowledge, there are two main axes of the RAAS: (1) angiotensin-converting enzyme (ACE)-angiotensin II-AT 1 receptor axis and (2) ACE2-angiotensin-(1-7)-Mas receptor axis. The activation of the first axis leads to deleterious effects, including vasoconstriction, endothelial dysfunction, thrombosis, inflammation, and fibrosis; therefore, blocking the components of this axis is a highly rational and commonly used therapeutic procedure. The ACE2-Ang-(1-7)-Mas receptor axis has a different role, since it often opposes the effects induced by the classical ACE-Ang II-AT 1 axis. Once the positive effects of the ACE2-Ang-(1-7)-Mas axis were discovered, the alternative ways of pharmacotherapy activating this axis of RAAS appeared. This article briefly describes new molecules affecting the RAAS, namely: recombinant human ACE2, ACE2 activators, angiotensin-(1-7) peptide and non-peptide analogs, aldosterone synthase inhibitors, and the third and fourth generation of mineralocorticoid receptor antagonists. The results of the experimental and clinical studies are encouraging, which leads us to believe that these new molecules can support the treatment of cardiovascular diseases as well as cardiometabolic disorders.

Angiotensin converting enzyme inhibitors and propofol both exert hypotensive action and may affect hemostasis. We investigated the influence of quinapril and propofol on hemodynamics and hemostasis in renal-hypertensive rats with induced arterial thrombosis. Two-kidney, one clip hypertensive rats were treated with quinapril (3.0 mg/kg for 10 days), and then received propofol infusion (15 mg/kg/h) during ongoing arterial thrombosis. The hemodynamic and hemostatic parameters were assayed. Quinapril exerted a hypotensive effect increasing after propofol infusion. Quinapril showed an antithrombotic effect with the platelet adhesion reduction, fibrinolysis enhancement and oxidative stress reduction. Propofol did not influence thrombosis; however, it inhibited fibrinolysis and showed prooxidative action. The effect of propofol on fibrinolysis and oxidative stress was significantly lower in quinapril-pretreated rats. Mortality was increased among rats treated with both drugs together. Our study demonstrates that pretreatment with quinapril reduced the adverse effects of propofol on hemostasis. Unfortunately, co-administration of both drugs potentiated hypotension in rats, which corresponds to higher mortality.

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Background: Identification and quantitative determination of cytisine, especially in biological samples and pharmaceutical formulations, is still a difficult analytical task. Cytisine is an alkaloid with a small and very polar molecule. For this reason, it is very weakly retained on reversed phase (RP) stationary phases, such as commonly used alkyl-bonded phases. The very weak retention of cytisine causes it to be eluted together with the components of biological matrices. Objective: Comparison and evaluation of various chromatographic systems for analysis of cytisine in different matrices—serum, saliva and pharmaceutical formulation—by high performance liquid chromatography (HPLC) with diode array (DAD), fluorescence (FLD) and mass spectrometry (MS) detection. Methods: The analyses were performed using HPLC in reversed phase (RP), hydrophilic interaction liquid chromatography (HILIC) and ion exchange chromatography (IEC) modes. Different sample pre-treatment methods were tested: Protein precipitation (with acetone, methanol (MeOH) or acetonitrile (ACN), and solid phase extraction (SPE) using cartridges with octadecyl (C18), hydrophilic-lipophilic balanced copolymer (HLB) or strong cation exchange sorbents (Strata X-C). Conclusion: Significant differences were observed in retention parameters with a change of the used chromatographic system. The various properties of stationary phases resulted in differences in analyte retention, peaks’ shape and systems’ efficiency. The weakest retention was observed using RP systems; however, the use of the Polar RP phase can be an alternative for application in green chromatography. In the strongest retention was observed using a strong cation exchange (SCX) phase. The most optimal systems were chosen for the analysis of cytisine in the pharmaceutical preparation, serum and saliva after sample pre-treatment with the new SPE procedure. Due to the sensitivity, the use of HPLC-DAD or HPLC-FLD is the most optimal for drug analysis in pharmaceutical preparations, whereas HPLC-MS is suitable for analysis of cytisine in biological samples.

This study identified anticonvulsant effects of arvanil, olvanil, AM 1172 and LY 2183240. The order of the magnitude of the anticonvulsant effects of the examined compounds was following: arvanil>olvanil>AM 1172>LY 2183240.