The use of new drugs with hypotensive action in late toxicosis of pregnancy

The problem of combating late toxicosis of pregnancy is still one of the most urgent.

Study of supramolecular complex of nifedipine with arabinogalactan on Wistar and ISIAH rats

Aim: Physicochemical and pharmacological study of the supramolecular inclusion complexes of the hypotensive drug nifedipine (NF) with the larch polysaccharide arabinogalactan (AG). Materials & methods: The NF:AG complexes were obtained and their physicochemical properties were studied. Their hypotensive action and pharmacokinetic profiles were evaluated in rats with normal and elevated arterial blood pressure. Results: In both rat lines the NF:AG complex decreased the arterial blood pressure at a lower dose than free NF (1.75 mg/kg of NF in complex compared with 3.5 mg/kg of free NF) and has a better pharmacokinetic profile than free NF. Conclusion: The use of the NF:AG complex is an effective way to sufficiently enhance and hasten NF’s hypotensive action.

Early Renal Vasodilator and Hypotensive Action of Epoxyeicosatrienoic Acid Analog (EET-A) and 20-HETE Receptor Blocker (AAA) in Spontaneously Hypertensive Rats

Cytochrome P450 (CYP-450) metabolites of arachidonic acid: epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE) have established role in regulation of blood pressure (BP) and kidney function. EETs deficiency and increased renal formation of 20-HETE contribute to hypertension in spontaneously hypertensive rats (SHR). We explored the effects of 14,15-EET analog (EET-A) and of 20-HETE receptor blocker (AAA) on BP and kidney function in this model. In anesthetized SHR the responses were determined of mean arterial blood pressure (MABP), total renal (RBF), and cortical (CBF) and inner-medullary blood flows, glomerular filtration rate and renal excretion, to EET-A, 5 mg/kg, infused i.v. for 1 h to rats untreated or after blockade of endogenous EETs degradation with an inhibitor (c-AUCB) of soluble epoxide hydrolase. Also examined were the responses to AAA (10 mg/kg/h), given alone or together with EET-A. EET-A significantly increased RBF and CBF (+30% and 26%, respectively), seen already within first 30 min of infusion. The greatest increases in RBF and CBF (by about 40%) were seen after AAA, similar when given alone or combined with EET-A. MABP decreased after EET-A or AAA but not significantly after the combination thereof. In all groups, RBF, and CBF increases preceded the decrease in MABP. We found that in SHR both EET-A and AAA induced renal vasodilation but, unexpectedly, no additive effect was seen. We suggest that both agents have a definite therapeutic potential and deserve further experimental and clinical testing aimed at introduction of novel antihypertensive therapy.

Heparin sensitization of fentanyl initiated mu-receptors

Heparin is an anticoagulant widely used in clinical practice. In addition to anticoagulant activity, heparin has a cytostatic, bacteriostatic, antilipemic, radioprotective effect, and exhibits antiallergic and hypotensive action. Heparin modulates cardiotropic, neurotropic, antihypoxic, anti-ischemic properties of regulatory peptides and pharmacological agents used in pain relief and anesthesia. At the same time, there is very little information about the antinociceptive effect of heparin. The aim of this work is to study the effect of heparin in combination with the opioid agonist fentanyl on mu-opioid receptors at the spinal and supraspinal levels. In experiments on laboratory rats, it was established that heparin, when pre-administered and combined with fentanyl, increases the latency in the tail flick test and the paw licking test. Naloxone, an opioid receptor antagonist, reduces antinociceptive efficacy of the studied compounds. Protamine sulfate also reduces the level of heparin sensitization of opioid receptors. Thus, the obtained data allow us to speak about the sensitizing effect of heparin on initiated by an agonist mu-opioid receptors at the spinal and supraspinal levels.

Multi-aspect approach to the optimization of pharmacotherapy of patients with arterial hypertension of high and very high risk

Introduction: Personalization of pharmacotherapy of cardiovascular diseases is one of the urgent problems of cardiology. Material and methods: The study includes 120 patients with grades 2-3 arterial hypertension with the criteria of high and very high risk of developing cardiovascular complications. The patients were randomized into three groups with differentstarting regimens of pharmacotherapy – fixed and free combinations of ACE inhibitors and dihydropyridine CCB. Evaluation of the efficacy, safety and individualization of a therapy was carried out by using pharmacokinetic, pharmacoeconomic, sonographic, and laboratory methods. Results and discussion: Antihypertensive treatment with the inclusion of Amlodipine and Lisinopril or Ramipril in patients with arterial hypertension, having a slow and very slow oxidative metabolism phenotype, is characterized by the development of a more pronounced hypotensive effect in this group of patients (p<0.05-0.001) (Δ% SBP from 12.7 to 24.6 and from 19.6 to 27.9, respectively; Δ% DBP from 10.6 to 19.1 and from 15.9 to 23.6, respectively) in comparison to the group of patients with a fast phenotype (Δ% SBP from 6.42 to 9.34; Δ% DBP from 1.04 to 5.66), which allows administering a personalized pharmacotherapy. For patients with arterial hypertension of high and very high risk, the use of a fixed combination of Amlodipine and Lisinopril as a basic variant of the two-four-component therapy compared with treatment options based on free combinations of the studied drugs provided a significantly more pronounced decrease in systolic blood pressure (24.9%, 17.8 %, 19.0%, respectively, p<0.01), a greater degree of regression of left ventricular myocardial hypertrophy (8.70%, 5.67%, 5.84%, respectively, p<0.05), significant (p<0.05-0.001) improvement in a number of parameters of the patients’ quality of life, and was characterized by the greatest economic efficiency according to various criteria of hypotensive action. Conclusion: The results obtained in the study demonstrate the advantages of a fixed combination over free combinations of antihypertensive drugs and demonstrate the possibility of a pharmacokinetic approach to individualization of pharmacotherapy.

New approach to molsidomine active metabolites coming from the results of 2 models of experimental cardiology

Molsidomine is a well-known vasodilatating, antianginal drug. Despite earlier studies with its metabolites (3-morpholino-syndnonimine (SIN-1) and N-nitroso-N-morpholino-amino-acetonitrile (SIN-1A)), which indicated a potential favorable cardioprotective activity, a lot of controversy remains. The aim of our research was to compare molsidomine, SIN-1, SIN-1A, and lidocaine influence on arrhythmias and hemodynamic parameters in 2 experimental models in rats. In the Langendorff heart study, SIN-1A markedly elevated left ventricular systolic pressure, maximum rise and fall of the first pressure derivative, coronary flow, and myocardial oxygen consumption. In addition, SIN-1A more so than SIN-1 significantly lowered creatine kinase release. The antiarrhythmic action of SIN-1 was observed, while lidocaine significantly diminished ventricular arrhythmias duration in comparison with the control. In the ischemia–reperfusion-induced arrhythmias model, hypotensive action of molsidomine was observed as well as the reduction in pressure rate product. Molsidomine also prolonged ventricular tachycardia duration. On the other hand, no significant effects on hemodynamic parameters as well as on ventricular arrhythmias were found in any of the SIN-1 and SIN-1A groups. In conclusion, our research suggests a possible direct, cardioprotective action of SIN-1A. It seems worthwhile to further investigate molsidomine derivatives, especially SIN-1A, because of its potential use in invasive cardiology procedures such as percutaneous transluminal coronary angioplasty.