Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension.

Our study aimed to examine the endothelium (vascular)-protecting effects of chronic cannabidiol (CBD) administration (10 mg/kg once daily for 2 weeks) in aortas and small mesenteric (G3) arteries isolated from deoxycorticosterone-induced hypertensive (DOCA-salt) rats and spontaneously hypertensive rats (SHR). CBD reduced hypertrophy and improved the endothelium-dependent vasodilation in response to acetylcholine in the aortas and G3 of DOCA-salt rats and SHR. The enhancement of vasorelaxation was prevented by the inhibition of nitric oxide (NO) with L-NAME and/or the inhibition of cyclooxygenase (COX) with indomethacin in the aortas and G3 of DOCA-salt and SHR, respectively.

Beneficial Changes in Rat Vascular Endocannabinoid System in Primary Hypertension and under Treatment with Chronic Inhibition of Fatty Acid Amide Hydrolase by URB597.

Our study aimed to examine the effects of hypertension and the chronic administration of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on vascular function and the endocannabinoid system in spontaneously hypertensive rats (SHR). Functional studies were performed on small mesenteric G3 arteries (sMA) and aortas isolated from SHR and normotensive Wistar Kyoto rats (WKY) treated with URB597 (1 mg/kg; twice daily for 14 days). In the aortas and sMA of SHR, endocannabinoid levels and cannabinoid CB receptor (CBR) expression were elevated.

Reduction of the serotonin 5-HT and 5-HT receptor-mediated contraction of human pulmonary artery by the combined 5-HT receptor antagonist and serotonin transporter inhibitor LY393558.

Background: LY393558 is a combined antagonist of serotonin (5-HT) 5-HT receptors and inhibitor of serotonin transporter (SERT). LY393558 reduces 5-HT-induced vasoconstriction and remodelling of rat and/or mouse pulmonary arteries. The aim of our study was to examine the effect of LY393558 on the 5-HT-stimulated vasoconstriction of human pulmonary arteries (hPAs) and to determine the underlying mechanism(s).

Functional and structural changes in aorta of mice divergently selected for basal metabolic rate.

Cardiovascular diseases (CVD) are one of the most common causes of mortality likely genetically linked to the variation in basal metabolic rate (BMR). A robust test of the significance of such association may be provided by artificial selection experiments on animals selected for diversification of BMR. Here we asked whether genetically determined differences in BMR correlate with anatomical shift in endothelium structure and if so, the relaxation and contraction responses of the aorta in mice from two lines of Swiss-Webster laboratory mice (Mus musculus) divergently selected for high or low BMR (HBMR and LBMR lines, respectively).

Vasodilatory effects of cannabidiol in human pulmonary and rat small mesenteric arteries: modification by hypertension and the potential pharmacological opportunities.

Objective: Cannabidiol (CBD) has been suggested as a potential antihypertensive drug. The aim of our study was to investigate its vasodilatory effect in isolated human pulmonary arteries (hPAs) and rat small mesenteric arteries (sMAs).

Methods: Vascular effects of CBD were examined in hPAs obtained from patients during resection of lung carcinoma and sMAs isolated from spontaneously hypertensive (SHR); 11-deoxycorticosterone acetate (DOCA-salt) hypertensive rats or their appropriate normotensive controls using organ bath and wire myography, respectively.

Modulation of Cardiovascular Function in Primary Hypertension in Rat by SKA-31, an Activator of and Channels.

The aim of this study was to investigate the hemodynamic effects of SKA-31, an activator of the small () and intermediate () conductance calcium-activated potassium channels, and to evaluate its influence on endothelium-derived hyperpolarization (EDH)-/ type relaxation in isolated endothelium-intact small mesenteric arteries (sMAs) from spontaneously hypertensive rats (SHRs). Functional in vivo and in vitro experiments were performed on SHRs or their normotensive controls, Wistar-Kyoto rats (WKY). SKA-31 (1, 3 and 10 mg/kg) caused a brief decrease in blood pressure and bradycardia in both SHR and WKY rats.

Nitric oxide as a modulator in platelet- and endothelium-dependent antithrombotic effect of eplerenone in diabetic rats.

We have recently demonstrated the antithrombotic effect of eplerenone on the arterial thrombotic process in diabetic rats associated with suppression of coagulation and enhancement of fibrinolysis. The aim of this study was to evaluate the role of platelets and endothelium in the mechanism of eplerenone antithrombotic action. Diabetes was induced in male Wistar rats with a single injection of streptozotocin (65 mg/kg).

Mechanisms of l-alpha-lysophosphatidylinositol-induced relaxation in human pulmonary arteries.

Aims: l-Alpha-lysophosphatidylinositol (LPI) is an endogenous agonist of G protein-coupled receptor 55 (GPR55) which relaxes mesenteric arteries on activation. The aim of the present study was to determine the influence and underlying mechanisms of LPI-induced relaxation in human pulmonary arteries (hPAs).

Main Methods: Functional studies were performed in isolated hPAs using organ bath technique.

Endocannabinoids modulate G protein-coupled receptor agonist-induced vasoconstriction via a negative feedback mechanism.

Objectives: The endocannabinoid (eCB) system centrally and peripherally regulates cardiovascular parameters, including blood pressure, in health and disease. The relationship between G protein-coupled receptor activation, regulation of eCBs release (mainly 2-arachidonoylglycerol) and subsequent CB receptor activation was initially observed in the central nervous system. Here, we review the latest findings from systemic physiological studies which include for the first time data from pulmonary arteries.

The influence of DOCA-salt hypertension and chronic administration of the FAAH inhibitor URB597 on K2.3/K3.1-EDH-type relaxation in rat small mesenteric arteries.

The aim of this study was to examine the influence of deoxycorticosterone acetate-salt (DOCA-salt) hypertension and chronic treatment with the fatty acid amide hydrolase inhibitor, URB597, on small and intermediate conductance calcium-activated potassium channels and endothelium-dependent hyperpolarization (K2.3/K3.1-EDH) in rat small mesenteric arteries (sMAs).

Activation of CB receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries.

Recent evidence suggests that endocannabinoids acting via cannabinoid CB receptors may modulate vascular responses of various vasoconstrictors in the rodent systemic vasculature. The aim of the study was to investigate whether endocannabinoids modulate the contractile responses evoked by a thromboxane A analog (U46619), angiotensin II (ANG II), serotonin (5-HT), and phenylephrine, which stimulate distinct G protein-coupled receptors (thromboxane, ANG II type 1, 5-HT, and α-adrenergic receptors) in isolated endothelium-intact human and rat pulmonary arteries (hPAs and rPAs, respectively). The CB receptor antagonist AM251 (1 μM) and diacylglycerol lipase (2-arachidonoylglycerol synthesis enzyme) inhibitor RHC80267 (40 μM) enhanced contractions induced by U46619 in hPAs and rPAs and by ANG II in rPAs in an endothelium-dependent manner.

Protective role of cannabinoid CB1 receptors and vascular effects of chronic administration of FAAH inhibitor URB597 in DOCA-salt hypertensive rats.

Aims: This study examined whether the fall in blood pressure (BP) induced by the chronic inhibition of fatty acid amide hydrolase (FAAH) by URB597 in deoxycorticosterone acetate (DOCA-salt) hypertensive rats correlates with endocannabinoid-mediated vascular changes.

Main Methods: Functional studies were performed in isolated endothelium-intact aortas and small mesenteric arteries (sMAs) using organ bath technique and wire myography, respectively.

Key Findings: In the DOCA-salt rats, methanandamide-stimulated relaxation was enhanced in sMAs or diminished in aortas.

[Serotonin hypothesis and pulmonary artery hypertension].

Pulmonary arterial hypertension (PAH) is a progressive, complex disease leading to the right ventricular failure and premature death. PAH is characterized by increased pulmonary arterial pressure, increased vascular resistance, pulmonary vascular remodeling and endothelial dysfunction. Pathomechanism of this disease is still unknown.

Mechanisms of endothelium-dependent relaxation evoked by anandamide in isolated human pulmonary arteries.

Endocannabinoids contract, relax or do not affect vessels with different calibre and tone in the pulmonary circulation in four species. The aim of the present study was to determine the mechanisms involved in the anandamide-induced relaxation of human pulmonary arteries (hPAs). Studies were performed in the isolated hPAs pre-constricted with the prostanoid TP receptor agonist, U-46619.

Relaxation of human pulmonary arteries by PPARγ agonists.

It has been suggested that activation of nuclear peroxisome proliferator-activated receptors γ (PPARγ) may represent a new strategy for the treatment of pulmonary arterial hypertension. It has been demonstrated that PPARγ activation relaxed the isolated mouse pulmonary artery. The aims of the present study were to examine whether and to which extent the two PPARγ agonists rosiglitazone and pioglitazone relax the isolated human pulmonary artery and to investigate the underlying mechanism(s).

Interleukin-13 gene polymorphisms in patients with Graves' disease.

Objective: In patients with Graves' disease (GD), an elevation of serum immunoglobulin E (IgE) has been recently reported to be associated with the severity of hyperthyroidism and ophthalmopathy. Interleukin 13 (IL-13) is a major cytokine involved in IgE synthesis and therefore may be a potential candidate gene contributing to the development of GD or influencing the clinical course of the disease.

Design: In a case-control study, we examined IL-13 gene single-nucleotide polymorphisms in the 5' promoter region at position -1112 (C to T change, termed as C-1112T) and in exon 4 at position 2044 (G to A change, G2044A, which results in an amino acid exchange Arg130Gln) in 261 patients with GD.