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The autonomic nervous system regulates internal organs and peripheral circulation, which enables the maintenance of homeostasis in vertebrate species. One of the brain regions involved in autonomic and endocrine homeostasis regulation is the paraventricular nucleus of the hypothalamus (PVN). The PVN is a unique site at which multiple input signals can be assessed and integrated. The regulation of the autonomic system by the PVN and, especially, the sympathetic flow, depends upon the integration of inhibitory and excitatory neurotransmitter action. The excitatory neurotransmitters such as glutamate and angiotensin II, and inhibitory neurotransmitters such as γ‑aminobutyric acid and nitric oxide, play a key role in the physiological function of the PVN. Moreover, arginine-vasopressin (AVP) and oxytocin (OXT) are important in the regulation of sympathetic system activity. The PVN is also crucial for maintaining cardiovascular regulation, with its integrity being pivotal for blood pressure regulation. Studies have shown that pre‑autonomic sympathetic PVN neurons increase blood pressure and the dysfunction of these neurons is directly related to elevated sympathetic nervous system activity under hypertension. Etiology of hypertension in patients is not fully known. Thus, understanding the role of PVN in the generation of hypertension may help to treat this cardiovascular disease. This review focuses on the PVN’s inhibitory and excitatory neurotransmitter interactions that regulate sympathetic system activity in physiological conditions and hypertension.

The impact of contaminated bottom sediments on plant growth and soil enzyme activities was evaluated in a greenhouse pot study. The sediments were moderately contaminated with zinc and heavily contaminated with polycyclic aromatic hydrocarbons and polychlorinated dibenzo-p-dioxins and furans. The sediments were mixed with soil and planted with either Festuca arundinacea or Tagetes patula. The capacity of two rhizobacterial strains (Massilia niastensis P87 and Streptomyces costaricanus RP92), previously isolated from contaminated soils, to improve plant growth under the chemical stress was tested. Application of sediments to soil was severely phytotoxic to T. patula and mildly to F. arundinacea. On the other hand, the addition of sediments enhanced the soil enzymatic activity. Inoculation with both bacterial strains significantly increased shoot (up to 2.4-fold) and root (up to 3.4-fold) biomass of T. patula. The study revealed that the selected plant growth-promoting bacterial strains were able to alleviate phytotoxicity of bottom sediments to T. patula resulting from the complex character of the contamination.

Aims This study was performed to examine whether hypertension affects the sympathetic transmission to resistance vessels of pithed rats via inhibitory presynaptic cannabinoid CB1 receptors and whether endocannabinoids are involved in this response. Materials and methods We compared uninephrectomised rats rendered hypertensive by high salt diet and deoxycorticosterone acetate (DOCA) injections with normotensive animals (uninephrectomy only). Experiments were performed on vagotomised and pithed animals. Increases in diastolic blood pressure (DBP) were induced four times (S1–S4) by electrical stimulation or phenylephrine injection. Key findings Electrical stimulation (0.75 Hz, 1 ms, 50 V, 5 impulses) of the preganglionic sympathetic nerve fibres innervating the blood vessels more strongly increased DBP in normotensive than in DOCA–salt rats. Phenylephrine (0.01 μmol/kg) induced similar increases in DBP in both groups. The cannabinoid receptor agonist CP55940 (0.01–1 μmol/kg) did not modify the rises in DBP induced by phenylephrine. However, it inhibited the electrically stimulated increases in DBP, more strongly in DOCA–salt than in normotensive animals (maximally by 50 and 30%, respectively). The effect of CP55940 was attenuated by the CB1 antagonist AM251 (3 μmol/kg). AM251 enhanced the neurogenic vasopressor response during S4 by itself in hypertensive rats only. URB597 (3 μmol/kg), which inhibits degradation of the endocannabinoid anandamide, did not modify the electrically stimulated increases in DBP. Significance The function of inhibitory presynaptic CB1 receptors on sympathetic nerves is enhanced in DOCA–salt hypertensive rats. Thus, the CB1 receptor-mediated inhibition of noradrenaline release from the sympathetic nerve fibres innervating the resistance vessels might play a protective role in hypertension.

Cannabinoids, the active ingredients of Cannabis sativa var. indica, have been used by humans as recreational and therapeutic agents for thousands of years. This group of substances also includes synthetic ligands and, synthesized in the body of humans and animals, endocannabinoids. The best known compound classified as an endogenous cannabinoid is anandamide. However, recent studies show that another compound of this group, 2-arachidonoylglycerol (2-AG), also performs many important functions in the organism. 2-Arachidonoylglycerol plays an important role in the regulation of the circulatory system via direct and/or indirect, through their metabolites, effects on blood vessels and/or heart. Accumulating evidence reveals that 2-AG is involved in the pathogenesis of various shocks and atherosclerosis. Thus, it may be a novel attractive therapeutic target. However, because of rapid metabolism and opposite effects dependent on the experimental model, the function of 2-AG still remains to be established.

The aim of this paper was to evaluation functional diversity in rhizosphere soils of new quality varieties of winter wheat cultivation in organic farming. Field experiments were carried out in 2017 and 2018. Twelve commercial winter wheat varieties were selected for testing: Arktis, Bellisa, Estivus, Fidelius, Hondia, Jantarka, KWS Ozon, Linus, Markiza, Ostka Strzelecka, Pokusa, and Rokosz. Winter wheat cultivars were chosen for their high yielding potential and good tolerance to fungal diseases. In the plant production conducted in accordance with the principles of organic farming, the selection of the best quality varieties is a key element of agrotechnics. The samples of rhizosphere soils were collected each year in two seasons: spring and summer. The basic parameters of soil biological activities and microbial biodiversity indicators were determined. The high variability of biological activity and functional diversity of rhizosphere soils in the growing season between particular varieties of winter wheat was observed. The rhizosphere soils from varieties such as Bellisa, Arktis, Jantarka, Fidelius, Ostka Strzelecka, Pokusa, Rokosz and KWS Ozon were characterized by high biological activity and functional biodiversity. On the other hand, the soils collected from the varieties Estivus, Fidelius, Jantarkaand Hondia were characterized by medium and low biological activity and biodiversity indices. The highest yield was found in winter wheat varieties such as Bellisa, Fidelius and Jantarka. The results of these analyses allows for a more complete characterization of the yield potential of the tested varieties and their suitability for cultivation in the conditions of organic farming, taking into account the biological activity of soils.

Background The aim of our study was (1) the pharmacological characterization of EP 3 receptors in human pulmonary arteries and (2) the examination of the potential involvement of these receptors in the regulation of neurogenic tachycardia in pithed rats. L-826266 served as the EP3 receptor antagonist. Methods Experiments were performed on isolated human pulmonary arteries and pithed rats. Results The prostanoid EP 1 /EP 3 receptor agonist sulprostone (1 nM – 100 μM) concentration-dependently contracted isolated human pulmonary arteries (pEC 50 , 6.88 ± 0.10). The EP 1 receptor antagonist SC 19920 (100 μM) did not affect the vasoconstriction induced by sulprostone, the TP receptor antagonist sulotroban (10 μM) only slightly attenuated the effects elicited by sulprostone > 3 μM, whereas L-826266 (10 μM) shifted its concentration-response curve to the right (apparent pA 2 value 6.18; incubation time 0.5 h). In rings exposed to L-826266 (0.1,1 or 10 μM) for 3 h, a concentration-dependent inhibitory effect against the sulprostone-induced vasoconstriction was obtained, yielding a Schild plot-based pA 2 value of 7.39. In pithed rats, sulprostone (10 – 1,000 nmol/kg), but not the IP/EP 1 receptor agonist iloprost (1-100 nmol/kg), inhibited the electrically evoked increase in heart rate (HR) dosedependently, maximally by at least 80%. L-826266 (3 μmol/kg) did not affect basal HR and diastolic blood pressure, but reduced the inhibitory effect of sulprostone 1,000 nmol/kg by about 20%. Conclusion EP 3 receptors (1) located postsynaptically strongly contract human pulmonary arteries and (2) located presynaptically on sympathetic nerve fibers supplying the heart of pithed rats strongly inhibit the neurogenic tachycardia.

The aim of our study was (1) the pharmacological characterization of EP(3) receptors in human pulmonary arteries and (2) the examination of the potential involvement of these receptors in the regulation of neurogenic tachycardia in pithed rats. L-826266 served as the EP(3) receptor antagonist.Experiments were performed on isolated human pulmonary arteries and pithed rats.The prostanoid EP(1)/EP(3) receptor agonist sulprostone (1 nM - 100 μM) concentration-dependently contracted isolated human pulmonary arteries (pEC50, 6.88 ± 0.10). The EP(1) receptor antagonist SC 19920 (100 μM) did not affect the vasoconstriction induced by sulprostone, the TP receptor antagonist sulotroban (10 μM) only slightly attenuated the effects elicited by sulprostone3 μM, whereas L-826266 (10 μM) shifted its concentration-response curve to the right (apparent pA(2) value 6.18; incubation time 0.5 h). In rings exposed to L-826266 (0.1, 1 or 10 μM) for 3 h, a concentration-dependent inhibitory effect against the sulprostone-induced vasoconstriction was obtained, yielding a Schild plot-based pA(2) value of 7.39. In pithed rats, sulprostone (10 - 1,000 nmol/kg), but not the IP/EP(1) receptor agonist iloprost (1-100 nmol/kg), inhibited the electrically evoked increase in heart rate (HR) dose-dependently, maximally by at least 80%. L-826266 (3 μmol/kg) did not affect basal HR and diastolic blood pressure, but reduced the inhibitory effect of sulprostone 1,000 nmol/kg by about 20%.EP(3) receptors (1) located postsynaptically strongly contract human pulmonary arteries and (2) located presynaptically on sympathetic nerve fibers supplying the heart of pithed rats strongly inhibit the neurogenic tachycardia.

Oxidative stress is involved in progression of hypertension therefore the influence on endocannabinoids level may be useful in pharmacotherapy. The increase in the main endocannabinoid - anandamide level may be attained by inhibition of FAAH –enzyme responsible for anandamide degradation. Therefore the aim of this study was to exam complex dependencies between endocannabinoid system and oxidative stress formation as well as consequences of observed changes in the liver of hypertensive rats [DOCA-salt] receiving URB597 - FAAH inhibitor. 4-5 weeks old rats after nephrectomy have been receiving DOCA twice weekly and replacement of drinking water with 1% NaCl solution for 6 weeks. One group of these rats was injected i.p. with URB597 (1 mg/kg b.w.) for last 14 days. It has been shown that URB597 given to hypertensive rats caused an increase in the level of AEA and expression of CB1, CB2 receptor as well as decrease in the level of 2-AG and the activity of FAAH and MAGL what was accompanied by an increase in free arachidonic acid. URB597 caused also the significant changes in liver redox status. The ROS, GSH, GSSG, vitamin A levels and activity Cu,Zn-SOD, CAT, GSH-T were increased, while the activity of GSH-Px, GSSG-R as well as the level of vitamin C, E were diminished in comparison to hypertensive rats. The antioxidant defense was changes also on transcriptional level. Results showed that URB597 administration enhanced level of Nrf2 and its activator - cJun and caused decrease in other Nrf2 activators [KAP1, p21, p62, ERK1/2, pERK1/2] and its inhibitors [Keap1, Bach1]. Moreover expression of HO-1 was decreased. The consequence of above disturbances in redox status was increase in oxidative damages of lipid (4-HNE, MDA, 8-isoprostanes), protein (dityrosine, tryptophane, carbonyl group) and DNA (8-OH dG). This work was supported by Ministry of Science and Higher Education grant No. 40/KNOW/2013.

The endocannabinoid anandamide exerts complex effects on the cardiovascular system [Malinowska et al., Br J Pharmacol, 2011]. Thus, rapid intravenous injection of anandamide and its stable analogue methanandamide in anaesthetized rats and mice induces typical triphasic changes. Phase I, the so-called BezoldJarisch reflex, is characterized by a rapid bradycardia and hypotension associated with a decrease in cardiac contractility and an increase in total peripheral resistance. Phase II is a brief pressor response associated with an increase in cardiac contractility and blood flow in the mesenteric and renal arteries. Phase III comprises a prolonged (lasting up to 10 min) and marked decrease in blood pressure, mesenteric and renal blood flow, a marked decrease in cardiac contractility and a slight decrease in heart rate and total peripheral resistance. Phase I is mediated via vanilloid TRPV1 receptors since it was induced also by the TRPV1 receptor agonist capsaicin (but not by the CB1 receptor agonist CP55940), blocked by the TRPV1 receptor antagonists capsazepine and ruthenium red (but not by the CB1 receptor antagonist rimonabant) and absent in TRPV1 / mice. Phase II consists of a peripheral component that is most probably located in blood vessels, is sensitive to nifedipine, ruthenium red and pentobarbitone and, hence, probably represents a Ca-dependent mode of action and a central component. The paraventricular nucleus of the hypothalamus (PVN) may contribute to the latter since a pressor effect was obtained after injection of anandamide, methanandamide or CP55940 (intraventricularly or directly into the PVN). This effect only occurred when the peripheral CB1 receptors were blocked by administration of CB1 receptor antagonists, including AM6545 that does not reach the brain. It was sensitive to adrenalectomy and counteracted by antagonists of CB1, NMDA, thromboxane A2 and b2adrenergic receptors [AM251 (directly into the PVN), MK-801, SQ29548 and ICI118551, respectively] suggesting that the latter four receptors are involved in the events ultimately leading to the anandamide-induced adrenal secretion of catecholamines. Importantly, the hypotensive effect of intravenously administered CP55940 was reversed into a hypertensive one in the presence of AM6545 and both responses were abolished by chemical lesion of the PVN by kainic acid. Phase III is mediated mainly by presynaptic inhibitory CB1 receptors located on the postganglionic (although a preganglionic localization cannot be excluded) sympathetic nerve endings innervating resistance vessels and heart. The CB1 receptor antagonist-sensitive inhibitory effect of these receptors was detected after electrical stimulation of the preganglionic sympathetic nerve fibres in pithed rabbits or rats or following injection of nicotine but not phenylephrine/noradrenaline or isoprenaline (increasing blood pressure and heart rate, respectively). The prolonged hypotension might also be related to the activation of CB1 and/or vanilloid TRPV1 receptors in the spinal cord or to a direct vasodilatation via O-1918 sensitive receptors. In conscious rats anandamide and methanandamide induced a brief pressor (phase II) response connected with renal and mesenteric vasoconstriction and hindquarters vasodilatation. In addition, higher doses of anandamide elicited an initial bradycardia, hypotension and hindquarters vasoconstriction (phase I). However, unlike in anaesthetized rats, none of the cannabinoids led to a prolonged hypotension (phase III). Cardiovascular effects of anandamide are changed under pathophysiological conditions. Thus, in anaesthetized rats myocardial ischemia enhanced phase I and reduced phase III whereas hypertension enhanced phase III. Acknowledgement: B.M. and E.S. would like to express their gratitude to Professor Manfred Gothert for his continuous encouragement extending over a time period of decades.

We have shown previously that the cannabinoid receptor agonist CP55940 microinjected into the paraventricular nucleus of the hypothalamus (PVN) of urethane-anaesthetized rats induces depressor and pressor cardiovascular effects in the absence and presence of the CB1 antagonist AM251, respectively. The aim of our study was to examine whether the hypotension and/or hypertension induced by CP55940 given into the PVN results from its influence on glutamatergic and GABAergic neurotransmission. CP55940 was microinjected into the PVN of urethane-anaesthetized rats twice (S1 and S2, 20 min apart). Antagonists of the following receptors, NMDA (MK801), β2-adrenergic (ICI118551), thromboxane A2–TP (SQ29548), angiotensin II–AT1 (losartan) or GABAA (bicuculline), or the NO synthase inhibitor L-NAME were administered intravenously 5 min before S2 alone or together with AM251. The CP55940-induced hypotension was reversed into a pressor response by AM251, bicuculline and L-NAME, but not by the other antagonists. The CP55940-induced pressor effect examined in the presence of AM251 was completely reversed by losartan, reduced by about 50–60 % by MK801, ICI118551 and SQ29548, prevented by bilateral adrenalectomy but not modified by bicuculline and L-NAME. Parallel, but smaller, changes in heart rate accompanied the changes in blood pressure. The bi-directional CB1 receptor-mediated cardiovascular effects of cannabinoids microinjected into the PVN of anaesthetized rats depend on stimulatory glutamatergic and inhibitory GABAergic inputs to the sympathetic tone; the glutamatergic input is related to AT1, TP and β2-adrenergic receptors and catecholamine release from the adrenal medulla whereas the GABAergic input is reinforced by NO.